Immunobiology Zeitschrift für Immunitätsforschung

E d i t o r s

E. D . ALBERT, M ü n c h e n • H . BRANDIS, B o n n • H . DEICHER, H a n n o v e r • A . DE WECK, B e r n • K . E l C H M A N N , H e i d e l b e r g • M . FELDMANN, L o n d o n • E. G L E I C H M A N N , A m s t e r ­d a m • K . H A V E M A N N , M a r b u r g • H . KIRCHNER, H e i d e l b e r g • E . K L E I N , S t o c k h o l m • W . KÖHLER, Jena • J. P. LEVY, Paris - K . RESCH, H e i d e l b e r g • G . RIETHMÜLLER, T ü b i n ­gen • K . O . ROTHER, H e i d e l b e r g • M . SELIGMANN, Paris • V . SCHIRRMACHER, H e i d e l ­berg • C . SORG, M ü n s t e r • G . F . SPRINGER, Evanston • C . STEFFEN, W i e n • R. T lMPL, M ü n ­chen • H . WAGNER, M a i n z • G . W l C K , I n n s b r u c k • R. ZlNKERNAGEL, Zürich

Assistant t o the E d i t o r s

D . GEMSA, H e i d e l b e r g

E d i t o r i a l A d v i s o r y B o a r d

F. A l U T l , R o m • J. F . BACH, Paris • H . BAENKLER, Er langen • H . BALNER, R i j s w i j k • H . V. BOEHMER, Basel • D . G . BRAUN, Basel - V . BRAUN, Tübingen • J. BROSTOFF, L o n ­d o n • T . DIAMANTSTEIN, B e r l i n • W . DRÖGE, H e i d e l b e r g • P. DUKOR, Basel • K . FEDERLIN, U l m • H . FINGER, K r e f e l d • E . GÜNTHER, F r e i b u r g • U . H A D D I N G , M a i n z • G . J. HÄMMERLING, K ö l n • K . U . HARTMANN, M a r b u r g • H . ZUR HAUSEN, F r e i b u r g • K . H A V E M A N N , M a r b u r g • M . HESS, B e r n • W . HlJMANS, R i j s w i j k • K . H U M M E L , F r e i b u r g • J. K A L D E N , H a n n o v e r • T . J. K I N D T , N e w Y o r k • E . K O W N A T Z K I , H e i d e l b e r g • M . KRUPE, F u l d a • E . KUWERT, Essen • K . LENNERT, K i e l • F . L I L L Y , N e w Y o r k • J. L l N D E N M A N N , Zürich • E . MACHER, Münster • H . METZGER, Bethesda, M d . • V . TER M E U L E N , W ü r z b u r g • H . J . MÜLLER-EBERHARD, L a Jolla • W . MÜLLER-RUCHHOLTZ, K i e l • H . PETERS, K ö l n • L . POLAK, Basel • O . PROKOP, B e r l i n • H . RAMSEIER, Zürich • W . RAPP, H e i d e l b e r g • J. P. REVILLARD, L y o n • M . RöLLINGHOFF, M a i n z • E . RÜDE, M a i n z • F . SCHEIFFARTH, Er langen • E . SCHÖPF, H e i d e l b e r g • H . G . SCHWICK, M a r b u r g * C. SORG, Münster • W . SPIELMANN, F r a n k f u r t • M . W . STEWARD, L o n d o n • N . T A L A L , San Francisco • G . UHLENBRUCK, K ö l n • J. DE VRIES, A m s t e r d a m • H . WARNATZ, Er langen • O . WERDE-L I N , Kopenhagen • P. WERNET, Tübingen

V o l u m e 156

Gustav Fischer Verlag • Stuttgart • New York • 1979

U n t v a r $ W M * -

München

ISSN Immunobiology * Zeitschrift für Immunitätsforschung • 0171-2985 © Gustav Fischer Verlag • Stuttgart • N e w York • 1979 Alle Rechte vorbehalten Gesamtherstellung: Druckerei Ungeheuer+Ulmer K G G m b H - I - Co Printed in Germany

Editorial C o m m e n t ,

Starting w i t h V o l u m e 156, 1979, the name of the «Zeitschrift für Immunitätsforschung» has been changed to

«Immunobiology »

The «Zeitschrift», founded i n 1909 b y Paul E h r l i c h , was the f i rs t i m m u n o l o g i c a l journa l to be publ ished i n the w o r l d . The journa l has a long- l ived reputat ion as being an i m p o r t a n t source of scientific i n f o r m a t i o n based on the contr ibut ions of famous immunologis ts . The increased use of Engl ish as the c o m m o n scientific language has n o w p r o m p t e d the E d i t o r i a l Board to change the t radi t ional Ger­m a n t i t le to « I m m u n o b i o l o g y » . W i t h this t i t le change the j o u r n a l emphasizes its internat ional character as a f o r u m f o r the publ i ca t ion of a variety of dif ferent articles i n the broad f ie ld of i m m u n o l o g y .

The E d i t o r i a l Board of I m m u n o b i o l o g y

Contents

Original Papers

A N D R E E S E N , R., M . M O D O L E L L , H . U . W E L T Z I E N , and P. G. M U N D E R : A l k y l - L y s o -phospholipid Induced Supression of Human Lymphocyte Response to Mitogens and Selective Ki l l ing of Lymphoblasts 498

A R E N D , P.: A n Auto-reactive A-l ike Ovarian Determinant Distinct f rom Xeno-reactive A-l ike Structures 410

ARGOV, S., A . POROS, and E. K L E I N : Cation Requirement of Natural, in Vi tro Generated and Antibody Dependent Ki l l ing Exerted by Human Lymphocytes 25

B E N C Z U R , M . , G Y . G Y Ö R F F Y , T. G A R A M , M . V A R G A , G Y . M E D G Y E S I , M . S A N D O R , and G. G Y . P E T R A N Y I : Correlation between Effector Lymphocytes in Natural and A n t i ­body-mediated Cytotoxicity 320

B E R T S C H M A N N , M . , B . S C H Ä R E N , and E. F. L U S C H E R : Correlation of in Vivo and in Vitro Immune Reactions Against the Intradermally Developing P-815 Mastocytoma in the Syngeneic Mouse 382

BLOCKSMA, N . , H . V A N D l J K , P. KORST, and J. M . WlLLERS: Cellular and Humoral

Adjuvant Act ivi ty of a Mistletoe Extract 309 B O L T Z - N l T U L E S C U , G. , and O . F Ö R S T E R : Differences in the Cytotoxic Effect of Rabbit

Anti-Rat Macrophage Sera on Rat Alveolar and Peritoneal Macrophages 331 B R A D E , V. , and G. K R E U Z P A I N T N E R : Interaction of Lipopolysaccharides and of L ip id A

from Yersinia Enterocolitica w i t h Purified Guinea Pig C 3 441

C Z A R N E T Z K I , B . M . , D . H A N N I C H , and H . N i E D O R F : In-vi tro Studies on the Develop­ment of Rat Peritoneal Mast Cells 470

D l E R i C H , M . P., B . L A N D E N , and M . SCHMITT: Complement Receptor Analogous Factors in Human Serum: I . Isolation of a Molecule Inhibitory for Complement Dependent Rosette Formation, its Identification as a , -Anti trypsin and its Functional Characterization 153

DRÖGE, W . : Hypothesis on the Origin of the Strong Alloreactivity 2

F A B R I C I U S , H.-A., and R . S T A H N : Human Primary T-Cell Lines in Lectin-freeMedia . . 364 F O R B E S , I . J., P. D . Z A L E W S K I , and B . D O E R K E N : A Simple Immunolatex Procedure for

Light and Fluorescence Microscopy 138

G A R R I D O , F., M . P E R E Z , M . D . T O R R E S , E. G A R C I A - O L I V A R E S , P. I V A N Y I , and V. S C H I R R M A C H E R : A Syngeneic A n t i Tumor Serum Recognizing a Complex H-2 Alloantigen 110

G O L S T E I N , P., B . R U B I N , F. D E N I Z O T , and M . F. L U C I A N I : Xenoserum-Induced Cyto­lytic «T» Cells: Polyclonal Specificity w i t h an Apparent «Anti-Self» Component, and Cooperative Induction 121

H A A S , I . G. , E. S I M O N , and W . G. B E S S L E R : Effect of the Aggregational State on the Mitogenicity of Lipoprotein from the Outer Membrane of Escherichia Coli 418

H A V L I C E K , J . , O . KÜHNEMUND, J . S R A M E K , and J . POKORNY: Isolation of Type-Specific Antibody to Streptococcus Pyogenes by A f f i n i t y Chromatography 48

K A K I U C H I , T. , H . NAR1UCHI, and T . M A T U H A S I : Specificity of an Ant i -Murine B Cell Serum 342

552 • Contents

K I R C H N E R , H . , H . H . P E T E R , H . M . H I R T , R. Z A W A T Z K Y , H . D A L Ü G G E , and P. B R A D S T R E E T : Studies of the Producer Cell of Interferon in Human Lymphocyte Cultures 65

K N Ö L L , H . , O . K Ü H N E M U N D , and J . H A V L f C E K : Mitogenic and Antigenic Properties of Group A Streptococcal M-Protein Preparations 537

K O S Z I N O W S K I , U . , D . G R E B E R , and I . N E U S C H A E F E R - R U B E : Generation of Virus Specific Cytotoxic T Cells in Vi t ro . I I I . Spleen Cells Stimulated by Viral Antigens Generate Alloreactive Cytotoxic T Cells 83

M A T Z K U , S., and M . Z ö L L E R : A Sandwich Isotopic Antiglobul in Assay. Application to the Detection of Antibodies in Non-SPF rats Bearing Spontaneous Tumors 483

M A U C H , H . , H . J . H A M M E R , and G. K ü M E L : A Long-lasting Enhancing Effect of A n t i -Tuberculin Antiserum on Delayed-type Hypersensitivity Reaction in BCG-infected Guinea Pigs 477

P T A K , W. , D . R Ö Z Y C K A , and M . R E W I C K A : Induction of Suppressor Cells and Cells Producing Antigen-Specific Suppressor Factors by Haptens Bound to Self Carriers . . 400

RAUTERBERG, E. W. , G. H Ä N S C H , and U . ROTHER: Isolation of Late Complement Components by Af f in i ty Chromatography. I I . Purification of the Human Comple­ment Component C6 142

R E S C H , K . , and D . G E M S A : The Role of Macrophages in the Activation of T -Lympho-cytes by Concanavalin A . I . Macrophages Support Proliferation after Commitment of Lymphocytes 509

D E RiDDER, G. , and L . B E R R E N S : Precipitating and Non-precipitating Complement Consuming IgG Subclass Antibodies in Pigeon Breeders'Disease 168

D E RiDDER, G. , A . G . V A N DlJK, and L . B E R R E N S : Complement Consuming Antibodies against a Modif ied Human Serum Protein in Pigeon Breeders' Disease 523

ROSZKOWSKI, W . , S. SZMIGIELSKI, M . JANIAK, and J . K . WREMBEL: Effect of Moderate (40 °C) and Intensive (43 °C) Hyperthermia on Spleen, Lymph-Node and Thymus-Derived Murine Lymphocytes in vitro 429

SlEBER, G. , and H . R U H L : Stimulation of Human and Mouse Lymphocytes by Ribo-somal Proteins 464

S I M O N , M . M . , and U . K O S Z I N O W S K I : Generation of Effector Cells f rom T Cell Subsets. I . Similar Requirement for L y t T Cell Subpopulations in the Generation of Alloreac­tive and H - 2 Restricted Killer Cells 96

S T E I N I T Z , M . , I . SEPPÄLÄ, K . E I C H M A N N , and G. K L E I N : Establishment of A Human Lymphoblastoid Cell Line w i t h Specific Antibody Production Against Group A Streptococcal Carbohydrate 41

U O T I L A , A . : Studies on the Chemical Nature of Dialysable Transfer Factor. Comparison of Human Leukocyte Dialysate and Dialysates Derived from Human Serum and from Mammalian Lymphoid and N o n - L y m p h o i d Organs 353

WAGNER, M . : Interaction of Wheat-germ Agglutinin w i t h Streptococci and Streptococ­cal Cell Wall Polymers 57

WEISS, S., K . H i L D , and D . G. B R A U N : Light Heterogeneity of Type X Anti-Streptococ-cal Group A-variant Polysaccharide Antibodies in Rabbits 35

W l C K , G . , R. W . G L A N V I L L E , and R. T i M P L : Characterization of Antibodies to Basement Membrane (Type IV) Collagen in Immunohistological Studies 372

WlESINGER, D . , and J . F. B O R E L : Studies on the Mechanism of Action of Cyclo­sporin A 454

W O L F F , M . H . , F. B Ü C H E L , and A . Z O L L : Serological Studies on the Antigenic Relation­ship between Herpes Simplex Virus and Varicella-Zoster Virus 76

W O O D Y , J . N . , S. H O W I E , and M . F E L D M A N N : Induction of Ant ibody Responses I n Vivo by Antigen Specific Helper Factor 13

Contents • 553

Abstracts

Symposium 1: Immunoendocrinology

I R V I N E , W . J . : Autoimmunity in diabetes mellitus 180 PlERPAOLI, W . , and G . MAESTRONI: Pineal function and bone marrow transplantation:

T w o examples of immune-endocrine network 179 S C H L E U S E N E R , H . , P. K o T U L L A , and B . W E N Z E L : Thyroid stimulating autoantibodies in

Graves' disease 181 VOISIN, G. A . : Types of immune response of the mother to the fetus 179

Symposium 2: Effector Mechanisms

S H E V A C H , E. M . : The role of the macrophage in the generation of T effector cells . . . . 183 R I E T H M Ü L L E R , G. , M . H A D AM, H . F E U C H T , J . G. S A A L , and I . W Ö L K - P U S C H E L : Natural

cytotoxicity in man 184 RöLLiNGHOFF, M . , K . P F I Z E N M A I E R , and H . W A G N E R : T - T cell cooperation in the

induction of murine cytotoxic T lymphocytes • 182 ZlNKERNAGEL, R. M . : Cell-mediated immunity to intracellular parasites and the biologi­

cal role of major transplantation antigens 182

Workshop Nr. 1: Ontogeny and Phylogeny of Immunity

A L B I N I , B . , I . G L U R I C H , and G . A . ANDRES: The effect of bursectomy and thymectomy on chronic serum sickness in the chicken 185

A R N D T , R., R. S T A R K , A . H A M A N N , and H . G . T H I E L E : Partial molecular characteriza­t ion of two newly detected T-axis differentiation antigens in the rat 185

B O Y D , R., and H . W A R D : Antigenic changes associated with chicken B lymphocyte differentiation 186

C Z A R N E T Z K I , B . M . , A . F E L D M A N N , and H . N i E D O R F : I n vitro development of rat mast cells f rom precursor cells 186

F E I G E , U . , M . M L Y N E K , L . - D . LEDER, and C. S O R G : Cytochemical studies on the differentiation of mononuclear phagocytes from human bone marrow in liquid culture 187

G A L L , P., and W . D R Ö G E : Development of cytotoxic T lymphocyte precursors in the absence of the thymus 188

J A N Z A R I K , H . , K . S C H A U E N S T E I N , and G. W l C K : Morphology and antigenic surface determinants of chicken lymphoid and thrombocytoid cells 188

K O N W A L I N K A , G. , C H . P E S C H E L , E. B O G U S C H , F . S C H M A L Z L , and H . B R A U N S T E I N E R : Colony types of human bone marrow cultures grown in agar under the influence of different sera 189

M O N N E R , D . A . , and P. F . MüHLRADT: In vitro evidence suggests a direct action of adjuvants on myeloid precursor cells in the bone marrow 189

Workshop Nr . 2: Clinical Relevance of New Immunological Methods

A L B I N I , B . , E. O S S I , E. P E N N E R , and G. A . A N D R E S : A micromethod for the detection of circulating immune complexes using Raji cells 191

ElFE, R. F . , and H . W . K R E T H : Impaired lymphocyte function in subacute sclerosing panencephalitis (SSPE) by using buffy coat cells instead of purified peripheral blood lymphocytes 191

554 • Contents

F I S C H E R , K . , and A . P O S C H M A N N : Quantitation of chord b lood-IgM and - I g A samples by fluoroimmunometric technique 192

G E I S E N , H . P., H . W . D O E R R , E. A D O L F , and G. E N D E R S : Rapid detection of I g M antibodies to rubellavirus and cytomegalovirus by elisa-technique 192

H A M M E R , H . J., G . K U M E L , M . H O F F M A N N , P. G . S C H E U R L E N , and H . M A U C H : A n enzyme-immunoassay for quantitation of human Ig 193

I N T O R P , H . W . , and H . L E Y S S E N S : Laser-nephelometry, a quantitative method to determine rheumatoid factors in paraproteinemias 193

L l M A N , W . , M . F R I C K E , and H . D E I C H E R : A Microtiter® conglutinin-binding RJA for detection of circulating immune complexes 194

R I N G , J., R. S I M O N , and C. A R R O Y A V E : I n vitro histamine release as possible indicator of contrast media hypersensitivity 194

S T E C H E M E S S E R , E., and P. A . B E R G : Differential diagnosis of cholestatic liver disease using a complement fixing PBC- and mixed form (MF)-specific subcellular antigen . . 196

S A Y E R S , T . J., K . H . W I E D M A N N , and P. A . B E R G : Demonstration of a trypsin insensitive subcellular antigen as a marker reacting only w i t h sera f rom a subgroup of patients w i t h cholestatic liver disease 195

S C H A U E N S T E I N , K . , G . B Ö C K , and G. W I C K : Laser immunofluorescence: Bleaching characteristics of F I T C conjugates specifically and non-specifically bound to antigen coated insoluble carriers 196

S P Ä T H , P., P. Y A M , and L . D . P E T Z : The radioactive antiglobulin test 197 S T E F F E N , C , L . S Ä N G E R , and J. M E N Z E L : Demonstration of antibodies to denatured type

I and type I I collagen in juvenile rheumatoid arthritis, Still's syndrome and controls by 1 4C-collagen radioimmunoassay 197

T E U B E R , J., K . H E L M K E , B. S C H I E S S E L , B. M I C H E L , and K . F E D E R L I N : The clinical relevance of Ig-classes and complement fixation of thyroid antibodies and immuno-complexes in various thyroid diseases 198

T E U B E R , J . , K . H E L M K E , M . U M B A C H , E. M A S E R , and K . F E D E R L I N : Comparative studies of various tests for the detection of thyroid antibodies, their sensitivity and specifi­city 198

T H U N O L D , S., R. M A T R E , and O . T 0 N D E R : Localization of cell markers in human lymphoid tissue 199

W O L F , H , and G . W l C K : Demonstration of anti-mucopolysaccharide (MPS) antibodies fol lowing treatment of patients w i t h glycosaminoglycan-polysulfate 199

Y u , M . - Y . , K . ULRICHS, and W . MüLLER-RuCHHOLTZ: N e w immunopharmacological approaches at modulation of reactivity in variously sensitized individuals 200

Workshop Nr . 3: Cellular Effector Mechanisms of Immunity

A R M E R D I N G , D . , H . R O S S I T E R , and P. M E Y E R : Effector mechanisms in the induced resistance against lethal herpes simplex type 2 (HSV2) infections in mice 201

B A R T E L E T T , R., R. S C H A W A L L E R , M . R Ö L L I N G H O F F , and H . W A G N E R : Cortical thymo­cytes lack immunocompetent T helper cells but not cytotoxic T lymphocyte precur­sors 201

E N G L E R , H . , R. Z A W A T Z K Y , H . B E C K E R , V . S C H I R R M A C H E R , and H . K I R C H N E R : Interferon production in the mixed lymphocyte culture ( M L C ) of the mouse 202

Z A W A T Z K Y , R , H . E N G L E R , J. H I L F E N H A U S , and H . K I R C H N E R : Interferon production induced in mouse spleen cells by herpes simplex virus (HSV). Correlation w i t h in vivo resistance to viral infection 202

H O N I G , T H . , H . - W . V O H R , and A . S C H I M P L : Studies on the generation and expression of H - 2 controlled T-helper function in chimeric mice 203

K U R R L E , R., R. S C H A W A L L E R , M . R Ö L L I N G H O F F , and H . W A G N E R : Herpes virus specific H - 2 D k restricted murine C T L are also cytotoxic towards noninfected target cells expressing the D d alloantigen 203

Contents • 555

L A N G , H . , W . D O M Z I G , and M . L . L O H M A N N - M A T T H E S : Cooperative effects between antibody-dependent and lymphokine-induced macrophage mediated cytotoxicity . . 204

L E I B O L D , W . , H . M . H I R T , H . K I R C H N E R , H . H . P E T E R , and R. Z A W A T Z K I : Relationship of spontaneous cell mediated cytotoxicity (SCMC) to interferon-induction in mixed lymphocyte reactions ( M L R ) w i t h normal and transformed lymphoid cells 204

M O E D D E R , E., H . E N G E R S , and J . L O U I S : Protozoan parasite-induced proliferative response of primed T lymphocytes 205

M Ö L L E R , G . , and W . K Ö N I G : Binding characteristics of aggregated IgGa to rat basophilic leukemia (RBL) cells and rat mast cells 205

M O S S M A N N , H . , B. S C H M I T Z , M . M E Y E R - D E L I U S , H U . W E L T Z I E N , and D . K. H A M M E R : Mast cell activation by crosslinking IgE receptor and antigenic determinants inserted into the l ipid phase of the membrane 206

P E T E R , H . H . , S. G E N D V I L I S , B. L A N G E , A . S E R B I N , S. E U L E R , W . S T A N G E L , H . J . A V E N A R I U S , and H . D E I C H E R : Natural ki l l ing ( N K ) in hemopoietic disorders and immunodeficiency syndromes: evidence for the bone marrow dependency of human N K effector cells 206

P F I Z E N M A I E R , K , M . R Ö L L I N G H O F F , H . R O D T , and H . W A G N E R : T-cell mediated cytotoxic immune reactivity 2 0 7

P F I Z E N M A I E R , K. , R. S C H A W A L L E R , and H . W A G N E R : Fine specificity and lytic activity of monoclonal alloreactive cytotoxic T lymphocytes 2 0 7

R U M P O L D , H , D . K R A F T , O . S C H E I N E R , P . M E I N D L , and G. B O D O : Enhancement of N K , but not K cell activity by different interferons 208

S C H M I T Z , B., H . M O S S M A N N , P. POSSART , and B. K. M O O K E R J E E : Role of oxidant generation in the effector mechanism of antibody-dependent neutrophil-mediated cytotoxicity 208

T H E O B A L D , K., H . W . H E N N , and W . K Ö N I G : Modulation of histamine release f rom rat mast cells and human basophils by serum factors 209

T O N Y , H . P., A . S C H I M P L , and E. W E C K E R : Stimulation of DNA-synthesis in murine B lymphocytes by anti-IG antibodies: dominance of a negative signal mediated by the Fc receptor 2 0 9

W A R N A T Z , H . , W . R Ö S C H , W . G E R L I C H , and W . G U T M A N N : Antibody-dependent cell-mediated cytotoxicity ( A D C C ) and cell-mediated cytotoxicity ( C M C ) to HBsAg-coated target cells in patients w i t h hepatitis B and chronic active hepatitis ( C A H ) . . . 210

W I E D E R M A N N , G. , O . S C H E I N E R , D . K R A F T , H . R Ü M P O L D , and H . S T E M B E R G E R : The influence of trypsin-treatment of effector cells on N K - and K-cell activity 211

W O L F , M . , W . SUESSMUTH, and W . D R Ö G E : Alternative modes of help for the induction of cytotoxic T lymphocytes 211

Workshop Nr . 4: Lymphocyte Subpopulations

B E R G E R , R., H . F R I S C H A U F , and W . K N A P P : Cortisol effects on suppressor cell activi­ties 213

B E S S L E R , W . , J . C Y B U L L A , A . F R E Y , and J . H i L L E M A N N : Bacterial cell surface compo­nents as B-lymphocyte mitogens: minimal structures required for mitogenicity . . . . 213

B I R K E , F. W . , E. P. R I E B E R , M . H A D A M , and G . R I E T H M U L L E R : Purified chicken antibodies against mouse unchain a n Q l M -̂chain fragments recognize crossreacting determinants on mouse T-lymphocytes 214

V A N ElJK, R. V . W . , and P. F. M U H L R A D T : Glycoproteins as markers of stimulated human lymphocyte subsets revealed by metabolic carbohydrate labelling 215

GATTRINGER, C , G . M l C H L M A Y R , and H . HUBER: Identification of two suppressor populations in human peripheral blood cells 215

H A M A N N , A . , R. A R N D T , and H . G . T H I E L E : Isolation and characterization of Thymus-Brain antigen (thy-analogue), a membrane glycoprotein f rom human brain 216

H A N S E N , E., and K. Z E I L L E R : Small lymphocyte populations in the bone marrow of rats and their thymus dependency 216

556 • Contents

J iLG, W . , and K . Z E I L L E R : Differences in surface protein patterns of three T cell subpopulations and B cell of the rat 2 1 7

KABELITZ, D . , U . F I N K , and A . REICHERT: Human M L C activated suppressor cells-enrichment on discontinuous density gradients 2 1 8

M O L D E N H A U E R , G . : Induction of suppressor T lymphocytes w i t h bordetella pertussis: effects of in vivo immunization w i t h pertussis on the mixed lymphocyte reaction (MLR) in mice 2 1 8

P I C H L E R , W . J., S. SHAW, and S. B R O D E R : Accessory cell requirement and mitogen induced proliferation of human T G and T M cell subsets 2 1 9

P I C H L E R , W . J., S. B R O D E R , S. M A R S H A L L , L . M U U L , and T. A . W A L D M A N N : Immuno-regulatory function of human T M and modulated T G cells 2 1 9

R E I M A N N , J., and T . D I A M A N T S T E I N : Syngeneic lymphoblasts induce T-stimulator cells in vivo acting in a syngeneic M L R in vitro 2 2 0

S T A H N , R., and H.-A. F A B R I C I U S : Modulation of growth factor (TCGF) dependent host T-cell proliferation by embryonal and neoplastic tissue in the human: Suppressor cell mediated regulation of T C G F production 221

S T Ö T T E R , H . , and E. R U D E : Genetic control of immune responses: presence of T helper cells in low responder mice 221

U L M E R , A . J., and H . - D . F L A D : Growth of T-lymphocyte colony forming units ( T L -CFU) f rom murine spleen cells stimulated by P H A in a one-stage agar micro culture . 221

Workshop N r . 5: Production and Characterization of Monoclonal Antibodies

A D O L F , G . R., E. H A R T T E R , H . R U I S , and P. S W E T L Y : Immunoadsorption of yeast catalase T using monoclonal antibodies 2 2 3

A N H O R N , G . , C. B R I T Z E L M E I E R , A . Z I E G L E R , and P. W E R N E T : The detection of a human thymocyte surface antigen ( H T A 1) on various leukaemic cells 2 2 3

B U R G E R , R., L . C L E M E N T , and E. M . S H E V A C H : Monoclonal antibodies to guinea pig cell surface antigens 2 2 4

G Ö T Z E , D . , and H . P. V O L L M E R S : Reactivity of monoclonal antibodies w i t h specificity against H - 2 antigens w i t h cells of inbred and w i l d mice 2 2 5

H E I N R I C H S , H , C. B R I T Z E L M E I E R , P. W E R N E T , and A . Z I E G L E R : Specificities of mono­clonal antibodies defined on human cell lines and leukaemic cells 2 2 5

L E M K E , H , and G. J. H Ä M M E R L I N G : Fine specificity analysis w i t h monoclonal anti­bodies of antigens controlled by the major histocompatibility complex ( H - 2 ) of the mouse 2 2 6

M A J D I C , O . , W . K N A P P , M . V E T T E R L E I N , W . R. M A Y R , and P. S P E I S E R : Hybridomas secreting monoclonal antibodies to human group A erythrocytes 2 2 6

R U M P O L D , H . , P. S W E T L Y , G . B O L T Z - N l T U L E S C U , and O . F Ö R S T E R : Monoclonal anti­bodies against macrophage associated antigens 2 2 7

W A L L I C H , R., and G . J. H Ä M M E R L I N G : The diversity of anti-phosphorylcholine anti­bodies analysed by monoclonal anti-idiotypes 2 2 7

Workshop Nr . 6: Histocompatibility Disease

B R A C K E R T Z , D . , W . M Ü L L E R , and P. W E R N E T : The genetic basis of rheumatoid arthritis: population and family studies 2 2 9

G R O S S , W . L . , I . V O R W E R K , E. C H R I S T O P H E R S , E. W E S T P H A L , and M . S C H L A A K : H L A -related control of T-cell responses in vitro in psoriasis 2 2 9

I N T O R P , H . W . , F. W E S S E L S , and H . L O S S E : Essential hypertension, a heritable disease linked to H L A - B 1 7 2 3 0

L A U D I E N , D . , D . B R A U N , W . R I E S E N , F. S C H U N T E R , and P. W E R N E T : Immunogenetic aspects of natural human immunity against infections w i t h group A streptococci . . . 2 3 0

Contents • 557

L U D W I G , H . , G . S C H E R N T H A N E R , H . S C H L E U S E N E R , B. W E N Z E L , P. K O T U L L A , and W . R. M A Y R : TSH-receptor and organ-specific autoantibodies in H L A - D R - t y p e d insu­lin-dependent diabetics 231

M U L L E R , G . , and P. W E R N E T : H L A - D R serology in transplantation 231 S C H E R A K , O . , J. S. S M O L E N , and W . R. M A Y R : Systemic lupus erythematosus (SLE) and

H L A - D R w 3 232 S M O L E N , J. S., O . S C H E R A K , E. J. M E N Z E L , and W . R. M A Y R : B-cell alloantigens in

rheumatoid arthritis (RA) 232 W E S T P H A L , E., U . LASSON, and W . M U L L E R - R U C H H O L T Z : Microabsorption studies of

non-crossreactive extra reactions of H L A antisera w i t h childhood leukemic cells . . . 233

Workshop N r . 7: Complement

B U B , F . , and M . L O O S : Ki l l ing of the Re- and S-form of Salmonella minnesota via the classical pathway of complement activation 234

D A M E R A U , B., and W . V O G T : Modification of leukocyte aggregation induced by the complement-derived peptides C3a and C5a and by formyl-methionyl-peptides . . . . 234

D E B A T I N , K. M . , and J. M E N Z E L : Phagocytosis associated release of lysosomal enzymes f rom granulocytes as a secretory process modulated by complement 235

K O F L E R , R., P. B E R G E R , and G . WlCK: Plaque-forming-cell assay in the chicken system: comparison of various developing techniques for lysis of antigen coated and uncoated erythrocytes 236

M E U R E R , M . , and I . G l G L I : Interaction of D N A w i t h the early components of comple­ment in the absence of antibody to D N A 236

MULLER, W. , and M . L O O S : Ant ibody independent complement mediated phagocytosis of trinitrophenylated sheep erythrocytes (E-TNP) 237

P A U S C H , V. , B. H A I D M A Y E R , M . KiRNBAUER, and W . R. M A Y R : Bf polymorphism in Vienna, Austria 237

P E N N E R , E., B. A L B I N I , G . A N D R E S , and F . M l L G R O M : Immunoglobulin as antigen in immune complex-mediated kidney diseases 238

P O D A C K , E. R.: Assembly of the membrane attack complex of complement 238 S C H O R L E M M E R , H . U . , H . H A N A U S K E - A B E L , and B. F . P O N T Z : Cartilage specific

collagen type I I activates mouse peritoneal macrophages and the alternative pathway of the complement system 239

S C H O R L E M M E R , H . U . , H . H A N A U S K E - A B E L , and B. F . P O N T Z : Activation of the alternative pathway of the complement system by different collagen types 239

S T E M B E R G E R , H . , G . W I E D E R M A N N , and G . M E I N G A S S N E R : Interaction of E. histolytica w i t h human complement 240

V O I G T L Ä N D E R , V. , G . M . H Ä N S C H , W . R Ö M E R , and U . R O T H E R : Studies on the pathogenesis of adverse drug reactions: Effects of acetylsalicylic acid on complement in vivo and in vitro 240

V O N Z A B E R N , I . , H . P R Z Y K L E N K , and W . V O G T : Comparison of activity and structure of Naja naja and Naja haje cobra venom factors: Detection of a correlation between binding of the 5 t h component of complement and its cleavage 241

Workshop Nr. 8: Self Recognition - Physiology and Pathology

L ' A G E - S T E H R , J.: Self recognition of Ig-associated structures on activated B-cells induce regulatory T-cell circuits 242

B E E R , M . , B. U . v. S P E C H T , and W . B R E N D E L : Characterization of basic encephalito-geneic protein coated nylon mesh adherent T cells by cytotoxic assay 242

B L A S E R , K. , T . N A K A G A W A , and A . L . DE W E C K : Suppression of murine Ig E directed to the benzylpenicilloyl (BPO) group w i t h isologous antiidiotypic antibodies in BALB/ C mice 243

558 • Contents

B O R N , W . , and H . W E K E R L E : I n vitro induction of self reactive T lymphocyte memory in cultures of syngeneic peanut agglutinin-negative mouse thymocytes and spleen cells . 243

B O Y D , R., K . S C H A U E N S T E I N , and G . W I C K : Characterization of effector cells in spontaneous autoimmune thyroiditis 244

F I N K , U . , P. A . P E T E R S O N , A . R E I C H E R T , A . M . F Ö D I N G E R , and C. H U B E R : IA- l ike antigens associated w i t h normal and neoplastic non-T cells induce autologous T lymphocyte proliferation 245

G E I S E R , M . , K . B L A S E R , and A . L . D E W E C K : Suppression of murine anti phosphoryl-choline (PC) Ig E by administration of isologous antiidiotypic antiserum against myeloma proteins 245

GLOBERSON, A . , and T. U M I E L : Recognition of self and modified self in aging 246 H E L M K E , K . , R. O T T E N , R. B R O C K H A U S , E. M A S E R , and K . F E D E R L I N : Correlation and

characterisation of islet-cell antibodies, circulating immune complexes and antinuclear antibodies in diabetic patients 246

H O H L F E L D , R., and H . W E K E R L E : In vitro generation of purified rat T-cell populations responsive against syngeneic antigen-specific secondary T-lymphocytes 247

K O L B , H . , U . K I E S E L , G . F R E Y T A G , and J. BlENER: Transfer of experimental diabetes by lymphocytes 248

K O L B - B A C H O F E N , V., and H . K O L B : Lectin-mediated recognition of neuraminidase-treated syngeneic lymphocytes by liver cells in vivo: induction of cellular autoimmune reactions 248

P O R Z S O L T , F., and H . H E I M P E L : Autoki l l ing of human lymphocytes in vitro 249 R E I M A N N , J., and R. D I A M A N T S T E I N : T-cell mediated in vivo proliferative response

elicited by polyclonally activated syngeneic or autologous lymphoblasts 249 S T O C K I N G E R , B., E . - M . L E M M E L , and U . B O T Z E N H A R D T : Further evidence for T cell

reactions of N Z B mice against M H C identical target cells 250 THOENES, G. H . , A . KRIEGER, and K . PlELSTICKER: Organ-specific alloimmune disease is

dissimilar to autoimmune disease 251 U L R I C H S , K . , D . D E L T Z , A . T H I E D E , and W . M U L L E R - R U C H H O L T Z : GVHR-induced, T

cell-mediated reactivity against self-constituents and inhibitory mechanisms 251 W E N Z E L , B., P. K O T U L L A , K . W . W E N Z E L , and H . S C H L E U S E N E R : Lymphocyte transfor­

mation test (LTT) w i t h solubilized TSH-receptor protein in Grave's disease (G.D.) . . 252 W l C K , G. , V. M U N R O , W . G E B H A R T , and R. T i M P L : Studies on the specificity of

autoantibodies to basement membrane in patients w i t h bullous pemphigoid 252 WlSSLER, J. H . : Activation of the kinin , complement and coagulation blood protein

systems by liposomes of selected structure: a model for endogenous pathways to non­specific tissue inflammation and auto-immune disease induced by primary messengers of tissue injury 253

Workshop Nr . 9: Macrophages

ANDREESEN, R., M . M O D O L E L L , V. SPETH, and P. G . M U N D E R : Human macrophage activation by alkyl-lysophospholipids 255

B O L T Z - N l T U L E S C U , G. , and O . F Ö R S T E R : Proteinase-treatment of rat macrophages induces binding of unsensitized sheep- and chicken-erythrocytes 255

HöRMANN, H . : Binding of fibronectin and denatured collagen by macrophages 256 K N O P , J.: Effect of vibrio cholerae neuraminidase on the action of macrophage released

mediators 257 L O M P E , S., H . K . M U L L E R - H E R M E L I N K , and W . M U L L E R - R U C H H O L T Z : Antimacrophage

antibodies: preliminary evidence for antibodies specific for reticulum cells in l y m ­phoid tissue 257

Loos , M . , W . M Ü L L E R , G . B O L T Z - N I T U L E S C U , H . R U M P O L D , and O . F Ö R S T E R : C l q , a subcomponent of the first component of complement, as a possible Fc receptor of peritoneal macrophages 258

Contents • 559

M E E R P O H L , H . - G . , and U . T R I T S C H L E R : Development of macrophage-mediated cyto­toxic capacities in fetal and neonatal mice 258

N A G A M U R A , Y . , and H . K O L B : Presence of a D-galactose/D-glucose specific lectin-like receptor on rat peritoneal macrophages 259

N E U M A N N , C , and C. SORG: Macrophages as targets for interferon inducers 259 O R O P E Z A - R E N D O N , R . L . , V. S P E T H , P. B A U D H U I N , and H . F I S C H E R : Inhibit ion of

pinocytosis of peroxidase in bone marrow macrophages by prostaglandin E t 260 O V E R W I E N , B., C H . N E U M A N N , and C S O R G : Use of synthetic, chromogenic substrates

for the detection of plasminogen activator(s) secreted by murine bone marrow derived macrophages 261

R i C H M A N , L . K., W . S T R O B E R , and J. A . B E R Z O F S K Y : H-2-l inked Ir Gene expression in determinant selection by murine Kupffer cells 261

SORG, C : Characterization of murine macrophage migration inhibitory activities (MIF) 262

SPAETH, E., and E. R U D E : Complementation of I r genes in responsiveness of mice to insulin and H - 2 restriction in macrophage - T cell interaction 262

S T E R N , A . C , P. E R B , and R. H . GiSLER: Helper T cell induction by bone-marrow macrophages 263

Workshop Nr . 10: Tumor Immunology

B E G E M A N N , M . , and G. C L A A S : Suppression of autologous mixed lymphocyte reactivity by serum from patients w i t h Hodgkin's disease 264

B E R T S C H M A N N , M . , and E. F. L U E S C H E R : The advantage of the intradermal over other routes of tumor cell injection to induce spontaneous tumor regression and the stimulation of an efficient immune response 264

BOSSLET, K. , and V. SCHIRRMACHER: Variability in the expression of tumor antigens on selected and nonselected murine tumor lines (Eb/ESb) w i t h different metastatic capacity 265

BRÜGGEN, J., W . H E L M I N G , C. SORG, and E. M A C H E R : Biochemical and serological characterization of cell surface structures and their correlation to the state of malig­nancy in human malignant melanoma 265

C l H A K , J., H . W . ZlEGLER, and E. KÖLSCH: T cell-mediated and humoral immune response of BALB/c mice against the syngeneic ADJ-PC-5 plasmocytoma 266

F A B R I C I U S , H.-Ä., R . S T A H N , and R. F E T T A : Impaired production of T cell growth factor (TCGF) in blood cells from tumor patients 266

G E M S A , D . , W . K R A M E R , G . T I L L , and K. R E S C H : Potentiation of macrophage mediated tumor cytostasis by ascites of tumor bearing mice 267

G R U B E R , F., C. H A M M E R , W . L . M A N G , W . B R E N D E L , and H . N A U M A N N : Immunologi­cal studies of patients w i t h carcinoma of the floor of the oral cavity and the tonsil . . . 268

H A R T H U S , H , R . J O H A N N S E N , and W . A x : Lymphocyte sensitization in tumor-bearing rats: E M T versus M L T C 268

A L - H A S H I M I , M . , T . KURATA, and M . MlCKSCHE: Immunoprophylaxis and immuno­therapy in Lewis lung tumor system 269

K A P P , J . -F. , and K. E l C H M A N N : In vivo anti-tumor effect of a factor in tumor ascites . . 270 K R A P F , E., W . L E I B O L D , H . H . P E T E R , and H . K I R C H N E R : Blocking effects of tumor-

cells and supernates of a human melanoma cell-line 270 M A I N U S C H , P., H . V. W A L L E N B E R G , J. M E Y E R , and C. H A M M E R : Enhancement of growth

of a virus-induced hamster-melanoma ( A - M E L 3) by suppressor cells 271 W A L L E N B E R G , H , P. M A I N U S C H , J. M E Y E R , and C. H A M M E R : Influence of spleen on

tumor growth in mice w i t h different spleen size 271 P E H A M B E R G E R , H . , F. G S C H N A I T , K. H O L U B A R , H . L U D W I G , and W . K N A P P : Monocyte

mediated antibody dependent cellular cytotoxicity in malignancies 272

560 • Contents

R ü H L , H . , M . B U R , and G . SlEBER: Pokeweed mitogen (PWM)-induced immunoglobu-lin-secreting cells (ISC) in patients w i t h Hodgkin's disease ( H . D . ) and N o n - H o d g k i n lymphomas ( N H L ) 273

S C H E D E L , L , D . P E E S T , K . S T Ü N K E L , M . F R I C K E , G . E C K E R T , and H . D E I C H E R : Idiotype bearing peripheral blood lymphocytes in human multiple myeloma and Walden­strom's macroglobulinemia 273

S C H U L Z , T . F . , M . P. D I E R I C H , E. Y E F E N O F , and G . K L E I N : Tumor-membrane-associated proteolytic activity mediating C3-dependent bridge formation between lymphocytes and tumor cells 274

S U T E R , L . , J. B R Ü G G E N , and E. M A C H E R : Characterization of melanoma associated antigens by use of rabbit heteroantisera 274

W E I N F U R T N E R , F . , C. H A M M E R , C. C H A U S S Y , J. S C H Ü L L E R , and W . W I E L A N D : Suppres­sor cell activity in the peripheral blood of patients w i t h carcinoma of the bladder and the kidney 275

ZöLLER, M . , and S. M A T Z K U : I n vitro characterization of anti-tumor effector mech­anisms in rats bearing spontaneous tumors 276

Workshop N r . 11: Clinical Slide Presentation

AUER, L . O . , and E. ZIEMER: Natural killer cell activity ( N K C A ) and antibody dependent cell mediated cytotoxicity ( A D C C ) in Crohn's disease (CD) 277

D E I C H E R , H , A . W R A B E T Z - W Ö L K E , and S. M A R G H E S C U : Therapeutic plasmapheresis in

severe pemphigus vulgaris (case report) 277 ElFE, R. F . : Cellular immunocompetence after transplantation of bone marrow incubated

w i t h anti-T-cell globuline 278 G A N G L , A . , J. S. S M O L E N , E. J. M E N Z E L , C. W O L F , and W . K N A P P : Suppressor cell

activity in patients w i t h inflammatory bowel disease 278 H A M M E R , C , W . L A N D , W . B U L L I N G E R , and W . B R E N D E L : In-vi t ro activation of

suppressor-cells in kidney transplant patients 279 L U D W I G , H . , G . S C H E R N T H A N E R , and H . P I E T S C H M A N N : Clinical and immunological

investigations in the first case of «benign» IgE-monoclonal gammopathy 280 M A I S C H , B . , R. T R O S T E L , P. A . B E R G , and K. K O C H S I E K : Role of antisarcolemmal

antibodies in cardiac diseases 280 P E T E R , H . H . , A . W R A B E T Z - W Ö L K E , U . M Ü L L E R - B A R T H E L , D . R O E L C K E , and K. F .

V Y K O U P I L : M . Waldenstrom w i t h cold agglutinin disease and leucopenia due to anti-«i» autoantibodies 281

P E T E R , H . H . , W . W R A B E T Z , H . J. A V E N A R I U S , and K. F . V Y K O U P I L : Combined immune

deficiency syndrome wi th Coombs positive anemia, thrombocytopenia and spleno-megalia 281

PiCHLER, W . J., S. B R O D E R , and T . A . W A L D M A N N : Modulation of immunoregulatory

function in vitro 282 S A L Z N E R , H . J., N . S C H M I E D E L , K. F . D R U S C H K Y , and J. R. K A L D E N : Concanavalin A

induced suppressor cells in the peripheral blood of patients w i t h myasthenia gravis and normal controls 283

S C H E R N T H A N E R , G. , H . L U D W I G , H . F R E Y L E R , and W . R. M A Y R : Circulating immune-

complexes, IgG-insulin antibodies, islet-cell antibodies and diabetic microangiopathy in type-I-diabetes mellitus 283

S M O L E N , J. S., E. J. M E N Z E L , O . S C H E R A K , W . K N A P P , and C. S T E F F E N : Clinical

relevance of circulating immune complexes in patients w i t h systemic lupus erythema­tosus and rheumatoid arthritis 284

S T I N G L , G . , L . G A Z Z E , N . C Z A R N E C K I , and K. W O L F F : Defective suppressor cells in

atopic dermatitis 284

Contents • 561

Workshop Nr . 12: Free Posters

A R R E N B R E C H T , S.: Differential metabolism of STH in normal and nude mice 286 A V E R D U N K , R., and T. G U N T H E R : C a + + - b i n d i n g , transport and ATPase-activities of

isolated lymphocyte plasma membranes 286 C A L A M I N U S , J. M . , J. B R Ü G G E N , and C. S O R G : Isolation, characterization and cultivation

of human trophoblastic cells 287 ElFE, G. , M . D E T A V E R A , and R. ElFE: Increased lymphokine (lymphotoxin) production

in leukocyte cultures upon delayed stimulation 287 G Ü R T L E R , L . G . , S. L E F R A N C , and H . C L E V E : The lectin binding sites of the plasma

membranes, of the mitochondrial membranes and the nuclear envelope of lympho-blastoid cells 288

H A L L F E L D , K . , J. S E I F E R T , G . F iGACZ, and W . B R E N D E L : Manipulation of the immune response by oral application of the antigen 289

H E D I N , H . , D . K R A F T , W . R I C H T E R , O . S C H E I N E R , and M . D E V E Y : Dextran reactive antibodies in patients w i t h anaphylactoid reactions to dextran 289

H Ü B N E R , L . , A . S C H I M P L , and E. W E C K E R : Biological characterisation of a goat anti-TRF-antiserum and its use in radioimmunoprecipitation 290

JÜPPNER , H . , H . M E Y E R z u S C H W A B E D I S S E N , H . M O H R , and R. D . H E S C H : Antibodies and peptides blocking the parathyroid hormone (PTH) receptor of renal plasma membranes 290

K O C H , N . , and D . H A U S T E I N : Studies of the association of membrane proteins of murine B lymphocytes by crosslinking and radiolabelling 291

K O F L E R , R., M . T A B E R E L L I , S. S C H W A R Z , H . W O L F , K . L O E W I T , and G . W I C K : Immunological dissection of rat pregnancy: characteristics of antisera to bovine prolactin 292

K R A U S - M A C K I W , E., W . M Ü L L E R - R U C H H O L T Z , and E. S C H Ö P F : Immune reactions in human genuine sympathetic ophthalmia 292

K R O E G E L , C , G . K R E T L , and W . K Ö N I G : Generation and release of an eosinophil chemotactic factor (ECF) by mellitin 293

L A N Z E R , G . , A . T . E N D L E R , C H . Z I E L I N S K I , and C. S T E F F E N : Inhibit ion of leukocyte locomotion by sera of patients w i t h rheumatoid arthritis 293

L E M M E L , E . - M . , V . M ö B U S , and U . B O T Z E N H A R D T : Activation of the immune system by inflammatory joint effusion and its pathophysiological consequence in rheumatoid arthritis 294

L I N K E , R. P.: Temperature-induced changes in the quarternary structure of serum amyloid A protein (SAA). Possible implications in the pathogenesis of «secondary» amyloidosis 295

M E N Z E L , E. J.: Association of collagen-like triple helices in C l q via hydrophobic interactions 295

M U L L E R , C , G . P A W E L E C , and P. W E R N E T : Serological and cellular heterogeneity of the H L A - D , - D R region in man 296

POSSART, P., B. S C H M I T Z , and H . M O S S M A N N : Evaluation of two functionally distinct

and independent mast cell responses 296 S C H M I D T - U L L R I C H , R., D . F. H . W A L L A C H , and J. L I G H T H O L D E R : T w o plasmodium

knowlesi-specific antigens on the surface of schizont-infected rhesus monkey erythro­cytes induce antibody production in immune hosts 297

S C H W A R Z , S., R. K O F L E R , M . T A B A R E L L I , and G. W l C K : Radioimmunological characteri­zation of antisera for immunological dissection of rat pregnancy 297

S E C C H I , A . G. , I . F R E G O N A , and F . D ' E R M O : «Lens permeability factors» in uveal immune inflammation 298

T E U B E R , J., K . H E L M K E , B. S C H I E S S E L , B. M I C H E L , and K . F E D E R L I N : The clinical relevance of Ig-classes and complement fixation of thyroid antibodies and immuncom-plexes in various thyroid diseases 299

562 • Contents

T I L L , G . , H . B R A U N , and D . G E M S A : Demonstration of chemotactic factor inactivator and cell directed inhibitor activity of neutrophil Chemotaxis in rats w i t h Arthus reactions 299

V E R M A , S. P., R. S C H M I D T - U L L R I C H , and D . F . H . W A L L A C H : State modifications of thymocyte plasma membrane proteins and lipids by mitogenic doses of concanavalin A : A Raman study on isolated membrane vesicles 300

W E N Z E L , K . W. , H . S C H L E U S E N E R , P. K O T U L L A , and B. W E N Z E L : Lymphokines as a marker for a cellular immune response in Grave's disease ( G . D . ) : Comparison of the direct and indirect LIF-test w i t h solubilized TSH-receptor protein 300

WlSSLER, J. H . , and M . A R N O L D : Large scale production, isolation and characterization of pig leucocyte-derived activities (lymphokines) affecting random migration (chemo-kinesis) and directional locomotion (Chemotaxis) of neutrophil, eosinophil and mono­nuclear leucocytes 301

W O T T G E , H . - U . , H . K . M U L L E R - H E R M E L I N K , and W . M U L L E R - R U C H H O L T Z : Develop­ment of immune reactivity. Does presensitization influence the lymphatic restitution after allogeneic bone marrow transplantation (BMT)? 302

W O R S T , P., P. B O U K A M P , V . S C H I R R M A C H E R , and N . E. F U S E N I G : Prolonged survival of allografted mouse epidermal cells; lack of la-antigens on mouse epidermal cells . . . . 303

Z l R M , M . : The keratitis disciformis, a reverse Wessely phenomenon. Experiments and clinical picture 304

Authors' Index

A D O L F , E . 2 . 4 * ) A D O L F , O . R . 5 . 1 L A G E - S T E H R , J . 8.1 A M E R D I N G , D . 3.1 A N D R E S , G . A . 1 . 1 , 2 . 1 , 7 . 8 A N D R E E S E N , R . 9 . 1 , 4 9 8 * * ) A N H O R N , G . 5.2 A L B I N I , B . 1 . 1 , 2 . 1 , 7 . 8 A L - H A S H I M I , M . 10.10 A R E N D , P. 4 1 0 A R G O V , S. 2 5 A R N D T , R . 1 . 2 , 4 . 6 A R N O L D , M . 12 .27 A R R E N B R E C H T , S . 12.1 A R R O Y A V E , C . 2.8 A U E R , J . 0 . 1 1 . 1 A V E N A R I U S , H . J . 11.9 A V E R D U N K , R . 12.2 A x , W . 10.9

B A R T E L E T T , R . 3.2 B A N D H A I N , P. 9 .10 B E E R , M . 8.2 B E G E M A N N , M . 10.1 B E N C Z U R , M . 320 B E R G , P. A . 2 . 9 , 1 1 . 7 B E R G E R , P. 7.4 B E R G E R , R . 4.1 B E R R E N S , L . 168, 523 B E R T S C H M A N N , M . 1 0 . 2 , 3 8 2 B E R Z O T S K Y , J . A . 9 .12 B E S S L E R , W. 4 . 2 , 4 1 8

BlENER, J . 8.11 B I R K E , F . W . 4 . 3 B L A S E R , K . 8 .3 , 8.7 B L O C K S M A , N . 309 B Ö C K , G . 2 .10 B O G U S C H , E . 1.8

B O L T Z - N l T U L E S C U , G . 5 .8 , 9 . 2 , 3 3 1

B O R E L , J. F. 454 B O R N , W . 8.4 B O N K A M P , P. 12 .29 B O S S L E T , K . 10.3 B O T Z E N H A R D T , U . 8 . 1 5 , 1 2 . 1 5 B O Y D , R . 1 . 3 ,8 .5 B R A C K E R T Z , D . 6.1 B R A D E , V . 441

B R A D S T R E E T , P. 6 5 B R A U N , D . 6 . 4 , 3 5 B R A U N , H . 12.24 B R A U N S T E I N E R , H . 1.8 B R E N D E L , W. 8 . 2 , 1 0 . 8 , 1 1 . 5 ,

12.6 B R I T Z E L M E I E R , C . 5 . 2 , 5 . 5 B R O C K H A U S , R . 8.9 B R O D E R , S . 4 . 1 1 , 1 1 . 1 0 B R Ü G G E N , J . 1 0 . 4 , 1 0 . 1 8 , 1 2 . 3 B U B , F . 7.1 B Ü C H E L , F . 76 B U L L I N G E R , W. 11.5 B U R , U . 10 .15 B U R G E R , R . 5.3

C A L A M I N U S , J . U . 12.3 C H A U S S Y , C H . 10.19 C H R I S T O P H E R S , E . 6.2 ClHAK, J . 10.5 C L A S S , G . 10.1 C L E M E N T , L . 5.3 C L E V E , H . 12.5 C Y B U L L A , J . 4.2 C Z A R N E C K I , N . 11.14

C Z A R N E T Z K I , B . 1.4, 470

D A M E R A U , B . 7.2 D A L U G G E , H . 65 D E B A T I N , K . M . 7.3 D E I C H E R , H . 1 0 . 1 6 , 1 1 . 1 2 D E L T Z , E . 8 .17 D E N I Z O T , F . 121 D E V E Y , U . 12.7 D I A M A N T S T E I N , T . 4 . 1 2 , 8 . 1 4 D I E R I C H , M . P. 1 0 . 1 7 , 1 5 3 V A N DijCK, G . 309, 523 D O E R K E N , B . 138 D O E R R , H . W . 2 . 4 D O M Z I G , W. 3.6 D R Ö G E , W . 1 . 6 , 2 D R U S C H K Y , K . F . 11.11

E C K E R T , G . 10.16 E I C H M A N N , K . 10 .11 ,41 E I F E , G . 12.4 E I F E , R . 12.4 E I F E , R . F . 2 . 2 , 1 1 . 3

V A N E I J K , R . V . W . 4 . 4 E N D E R S , G . 2.4 E N D L E R , A . T. 12.14 E N G L E R , H . 3.3 E N G E R S , H . 3.8 E R B , P. 9 .15 D ' E R M O , F . 12 .22

F A B R I C I U S , H . A . 4 . 1 3 , 1 0 . 6 , 364

F E D E R L I N , K . 12.23 F E I G E , U . 1.5 F E L D M A N N , A . 1.4 F E L D M A N N , U . 13 F E T T A , R . 10.6 F E U C H T , H . Symp. 1.3 F I G A C Z , G. 12.6 F I N K , U . 4 . 9 , 8 . 6 F I S C H E R , H . 9 .10 F I S C H E R , K . 2.3 F L A D , H . D . 4 . 1 5 F Ö D I N G E R , A . U . 8.6 F Ö R S T E R , 0 . 5 . 8 , 9 . 2 , 3 3 1 F O R B E S , J . 138 F R E G O N A , J . 12.22 F R E Y , A . 4 .2 F R E Y L E R , H . 11.12 F R E Y T A G , G . 8.11 F R I C K E , U . 2 . 7 , 1 0 . 1 6 F R I S C H A U F , H . 4.1 F U S E N I G , N . E . 12.29

G A L L I , P. 1.6 G A N G L , A . 11.4 G A R A M , T . 3 2 0 G A R C I A - O L I V A R E S , E . 110 G A R R I D O , F . 110 G A T T R I N G E R , C . 4.5 G A Z Z E , L . 11.14 G E B H A R T , W . 8 .19 G E I S E N , H . P. 2.4 G E I S E R , U . 8.7 G E M S A , D . 1 0 . 7 , 1 2 . 2 4 , 5 0 9 G I G L I , J . 7.5 GiSLER, R . H . 9 .15 G L A N V I L L E , R . W . 372 G L O B E R S O N , A . 8.8 G L U R I C H , J . 1.1

*) These numbers refer to Abstract numbers of the meeting of the Society for Immunology. **) Page numbers of Original Articles.

564 • Authors ' Index

G Ö T Z E , D . 5.4 G O L S T E I N , P . 121 G R E B E R , D . 83 G R O S S , W . L . 6.2 G R U B E R , F . 10.8 G S C H N A I T , F . 10.14 G Ü N T H E R , T . 12.2 G Ü R T L E R , L . G . 12.5 G Y Ö R F F Y , G Y . 3 2 0

H A A S , J . 6 , 4 1 8 H A D A M , M . Symp. 2 . 4 , 4 . 3 H Ä M M E R L I N G , G . J . 5.6, 5.9 H Ä N S C H , G . M . 7 . 1 2 , 1 4 2 H A I D M A Y E R , B . 7.7 H A L L F E L D , K . 12.6 H A M A N N , A . 1 .2 ,4 .6 H A M M E R , C. 1 0 . 8 , 1 0 . 1 3 ,

10 .19 ,11 .5 H A M M E R , H . J . 2 . 5 , 4 7 7 H A N A U S K E - A B E L , H . 7.10 H A N N I C H , D . 470 H A N S E N , E. 4 .7 H A R T H U S , H . 10.5 H A R T T E R , E. 5.1 H A V L I C E K , J . 4 8 , 5 3 7 H A U S T E I N , D . 12.10 H E D I N , H . 12.7 H E I M P E L , H . 8.13 H E I N R I C H S , H . 5.5 H E L M I N G , W . 10.4 H E L M K E , K . 8.9 H E S C H , R . D . 12.9 H I L D , K . 35 H I L F E N H A U S , J . 3.3 H I R T , H . M . 3 . 7 , 6 5 H Ö R M A N N , H . 9.3 H O F F M A N N , U . 2 .5 H O H L F E L D , R . 8 .10 H O L U B A R , K . 10.14 H O W I E , S. 13 H U B E R , H . 4 .5 H Ü B N E R , L . 12.8 H Ü N I G , T H . 3.4

I N T O R P , H . W . 2 . 6 , 6 . 3 J A N I A K , M . 429 I R V I N E , W . J . Symp. 1.3 J A N Z A R I K , H . 1.7 J lLG, W . 4.8 J O H A N N S E N , R . 10.9 JUPPNER, H . 12.9

K A B E L I T Z , D . 4 .9 K A K I U C H I , T . 342 K A L D E N , J . R . 11.11 K A P P J . F . 10.11

K I E S E L , U . 8.11 K I R C H N E R , H . 3 . 3 , 3 . 7 , 1 0 . 1 2 ,

65 K I R N B A U E R , U . 7.7 K L E I N , E. 2 5 K L E I N , G . 10 .17 ,41 K N A P P , W . 4 . 1 , 5 . 7 , 1 1 . 4 ,

11.13 K N Ö L L , H . 5 3 7 K N O P , K . 9.4 K O C H , N . 12 .10 K O C H S I E K , K . 11.7 K Ö L S C H , E . 10.5 K Ö N I G , W . 12.13 K O F L E R , R . 7 . 4 , 1 2 . 1 1 , 1 2 . 2 1 K O L B , H . 8.11, 8 . 1 2 , 9 . 8 K O L B - B A C H O F E N , U . 8 .12 K O N W A L I N K A , G . 1.8 K O R S T , P . 309 K O S Z I N O W S K I , U . 8 3 , 9 6 K O T U L L A , P . Symp. 2 .2 , 6 .5 ,

8 . 1 8 , 1 2 . 2 6 K R A F T , D . 12.7 K R A M E R , W . 10.7 K R A P F , E. 10 .12 K R A U S - M A C K , W . E. 12 .12 K R E I L , G . 12.13 K R E T H , H . W . 2.2 K R E U Z P A I N T N E R , G . 441 K R I E G E R , A . 8 .16 K R O E G E L , C. 12 .13 K Ü H N E M U N D , 0 . 4 8 , 5 3 7 KüMEL, G . 4 7 7 K U M E L , O . 2.5 K U R A T A , T . 10.10 K U R R L E , R . 3.5

L A N C E R , G . 12.14 L A N D , W . 11.5 L A N D E N , B . 153 L A N G , H . 3.6 L A S S O N , U . 6.9 L A U D I E N , D . 6.4 L E D E R , L . - D . 1.5 L E F R A N C E , S. 12.5 L E I B O L D , W . 3 . 7 , 1 0 . 1 2 L E M K E , H . 5.6 L E M M E L , E. M . 8 . 1 5 , 1 2 . 1 5 L E Y S S E N S , H . 2.6 L I G H T H O L D E R , J . 12.20

L l M A N , W . 2 . 7 L I N K E , R . P . 12.16 L O E W I T , K . 12.11 L O H M A N N - M A T T H E S , M . L .

3.6 L O M P E S , S. 9.5

L o o s , M . 7 . 1 , 7 . 6 , 9 . 6 L O S S E , H . 6.3 Louis , J . 3.8 L U C I A N I , M . F . 121 L U D W I G , H . 6 . 5 , 1 0 . 1 4 , 1 1 . 6 ,

11 .12

L U E S C H E R , E. F . 3 8 2

M A C H E R , E. 1 0 . 4 , 1 0 . 1 8 M A E S T R O N I , G . Symp. 1.2 M A S E R , E. 8.9 M A I N U S C H , P . 10.13 M A I S C H , B . 11.7 M A J D I C , J . 5 .7 M A N G , W . L . 10.8 M A R G H E S C U , S. 11.2 M A R S H A L L , S. 4 .11 M A T U H A S I , T . 342 M A T Z K U , S. 1 0 . 2 0 , 4 8 3 M A U C H , H . 2 .5 , 4 7 7 M A Y R , W . R . 5.7, 6 .5 , 6 .7, 6.8,

7 . 7 , 1 1 . 1 2 M E D G Y E S I , G Y . 3 2 0 M E E R P O H L , H . G . 9 .7 M E I N G A S S N E R , G . 7.11 M E N Z E L , E. J . 6 . 8 , 1 1 . 4 , 1 1 . 1 3 ,

12 .17 M E N Z E L , J . 7.3 M E U R E R , U . 7.5 M E Y E R , J . 10.13 M E Y E R , P . 3.1

M E Y E R z u S C H W A B E D I S S E N , H . 12.9

M E Y N E K , U . 1.5 M I C H E L , B . 12.23 M l C H E L M A Y R , G . 4.5 MlCKSCHE, U . 10 .10 M O D O L E L L , U . 9 .1 , 498 M Ö B I U S , V . 12.15 M O E D D E R , E. 3.8 M O H R , H . 12.9 M O L D E N H A U E R , G . 4 . 1 0 M O N N E R , D . A . 1.9 M O S S M A N N , H . 12 .19 M U H L R A D T , P . F . 1 . 9 , 4 . 4 M Ü L L E R , C. 12.18 M Ü L L E R , G . 6.6 M Ü L L E R , W . 6 . 1 , 7 . 6 , 9 . 6 M U L L E R - B A R T H E L , U . 11.8 M Ü L L E R - H E R M E L I N K , H . K .

9 . 5 , 1 2 . 2 8 M Ü L L E R - R U C H H O L T Z , W .

6.9, 8.17, 9 . 5 , 1 2 . 1 2 , 12.28 M U N D E R , P . G . 9 . 1 , 4 9 8 M U N R O , V . 8 .19 M U U L , L . 4 . 1 1

Authors ' Index • 565

N A G A M U R A , J . 9.8 N A K A G A W A , T . 8.3 N A R I U C H I , H . 342 N A U M A N N , H . 10.8 N E U M A N N , C H . 9 . 9 , 9 . 1 1 N E U S C H A E F F E R - R U B E , I . 83 N A U M A N N , H . 10.8 N I E D O R F , H . 1 . 4 , 4 7 0

O R O P E Z A - R E N D O N , 9 .10 O S S I , E . 2 . 1 O T T E N , R . 8.9 O V E R W I E N , B . 9.11

P A U S C H , U . 7.7 P A W E L E C , G . 12.18 P E E S T , P . 10.16 P E H A M B E R G E R , H . 10.14 P E N N E R , E . 7.8 P E R E Z , M . 110 P E S C H E L , C H . 1.8 P E T E R , H . H . 3 . 7 , 1 0 . 1 2 , 1 1 . 8 ,

1 1 . 9 , 6 5 P E T E R S O N , P . A . 8.6 P E T R A N Y I , G . 3 2 0 P F I T Z E N M A I E R , K . Symp. 2.2 P I C H L E R , W . J . 4 . 1 1 , 1 1 . 1 0

PlELSTICKER, K . 8.16 P I E R P A O L I , V . Symp. 1.2 P I E T S C H M A N N , H . 11.16 P O D A C K , E . R . 7.9 P O K O R N Y , J . 48 P O N T Z , B . F . 7 .10 P O R O S , A . 2 5 P O R Z S O L T , F . 8.13 P O S C H M A N N , A . 2.3 POSSART, P . 12.19 P R Z Y K L E N K , H . 7.13 P T A K , W . 400

R A U T E R B E R G , E . D . 142 R E I C H E R T , A . 4 . 9 , 8 . 6 R E I M A N N , J . 4 . 1 2 , 8 . 1 4 R E S C H , K . 1 0 . 7 , 5 0 9 R E W I C K A , U . 400 R I C H M A N , L . K . 9 .12 R I C H T E R , W . 12.7 D E R I D D E R , G . 1 6 8 , 5 2 3 R I E B E R , E . P . 4.3 R I E S E N , W . 6.4 RlETHMULLER, G . Symp. 2 .4,

4.3

R I N G , J . 2.8 R O E L C K E , D . 11.8 R Ö L L I N G H O F F , M . Symp. 2 .2 ,

3 . 2 , 3 . 5

R Ö M E R , W . 7.12 R O S S I T E R , H . 3 .10 R O S Z K O W S K I , W . 4 2 9 R O T H E R , U . 7 . 1 2 , 1 4 2 R O Z Y C K A , D . 400 R U B I N , B . 110 R U D E , E . 4 . 1 4 , 9 . 1 4 RUHL, 1 0 . 1 5 , 4 6 4 Ruis, H . 5 . 1 R U M P O L D , H . 5.8

S A A L , J . G . S y m p . 2.4 S A L Z N E R , H . J . 11.11 S A N D O R , M . 3 2 0 S A Y E R S , T . J . 2.9 S C H Ä R R E N , B . 382 S C H A U E N S T E I N , K . 1 .7 ,2 .10 ,

8.5

S C H A W A L L E R , R. 3 . 2 , 3 . 5 S C H E D E L , 1 .10 .16 S C H E I N E R , 0 . 1 2 . 7 S C H E R A K , O . 6 . 7 , 6 . 8 , 1 1 . 1 3 S C H E R N T H A N E R , G . 6 . 5 , 1 1 . 6 ,

11.12

S C H E U R L E N , P. G . 2.5 S C H I E S S E L , B . 12.23 S C H I M P L , A . 3 . 4 , 1 2 . 8 S C H I R R M A C H E R , V . 3 . 3 , 1 0 . 3 ,

12.29 S C H L A A K , M . 6.2 S C H L E U S E N E R , H . S y m p . 1.4,

6 . 5 , 8 . 1 8 , 1 2 . 2 6 S C H M A L Z L , F . 1.8 S C H M I D T - U L L R I C H , R. 12.20,

12.25 S C H M I E D E L , N . 11.11 S C H M I T T , U . 153 S C H M I T Z , B . 12.19 S C H Ö P F , E . 12.12 S C H O R L E M M E R , H . U . 7.10 S C H Ü L L E R , J . 10.19 S C H U L Z , T . F . 10 .17

S C H U N T E R , F . 6.4 S C H W A R Z , S. 12 .11 ,12 .21 S E C C H I , A . G . 12.22 S E I F E R T , J . 12.6 SEPPÄLA, J . 41 SHAW, S. 4.11

S H E V A C H , E . M . S y m p . 2 .3 , 5.3

SlEBER, G . 1 0 . 1 5 , 4 6 4 S I M O N , E . 4 1 8 S I M O N , M . M . 9 6 S I M O N , R. 2.8 S M O L E N , J . S . 6 . 7 , 6 . 8 , 1 1 . 4 ,

11.13

S O R G , C . 1 . 5 , 9 . 9 , 9 . 1 1 , 9 . 1 3 , 1 0 . 4 , 1 2 . 3

S P A E T H , E . 9 .14 V O N S P E C H T , B . U . 8.2 SPEISER, P . 5.7 S P E T H , V . 9 . 1 , 9 . 1 0 S R A M E K , J . 48 S T A H N , R . 4 . 1 3 , 1 0 . 6 , 364 S T A R K , R . 1.2 S T E C H E M E S S E R , E . 2 .9 S T E F F E N , C . 1 1 . 1 3 , 1 2 . 1 4 S T E I N I T Z , M . 41 S T E M B E R G E R , H . 7.11 S T E R N , A . C . 9 . 1 5 S T I N G L , G . 11.14 S T O C K I N G E R , B . 8 .15 S T Ö T T E R , H . 4 .14 S T R O B E R , W . 9 .12 S T Ü N K E L , K . 10.16 S U T E R , L . 10.18 S W E T L Y , P . 5 . 1 , 5 . 8

S Z M I G I E L S K I , S. 4 2 9

T A B A R E L L I , U . 12 .11 ,12 .21 T A P P E I N E R , G . 11 .12 T A V E R A D E , U . 12.4 T E U B E R , J . 12.23 T H I E D E , A . 8 .17 T H I E L E , H . G . 1 . 2 , 4 . 6 T H O E N E S , G . H . 8 .16 T I L L , G . 1 0 . 7 , 1 2 . 2 4 T I M P L , R . 8 . 1 9 , 3 7 2 T O R R E S , D . 110 T R I T S C H L E R , U . 9 .7 T R O S T E L , R . 11.7

U L M E R , A . J . 4 . 1 5 U L R I C H S , K . 8 .17 U M I E L , T . 8.8 U O T I L A , A . 353

V A R G A , U . 320 V E R M A , S . P . 12.25 V E T T E R L E I N , U . 5 .7 V O G T , W . 7 . 2 , 7 . 1 3 V O H R , H . W . 3.4 V O I G T L Ä N D E R , V . 7 .12 V O I S I N , G . A . Symp. 1.1 V O L L M E R S , H . P . 5.4 V O R W E R K , J . 6.2 V Y K O U P I L , K . F . 1 1 . 8 , 1 1 . 9

W A G N E R , H . Symp. 2 . 2 , 3 . 2 , 3.5

W A G N E R , U . 57 W A L D M A N N , T . A . 4 . 1 1 , 1 1 . 1 0

566 • Authors ' Index

W A L L A C H , D . F . H . 12.20, 12.25

V O N W A L L E N B E R G , , H . 10 .13 W A L L I C H , R. 5.9 W A R D , H . 1.3 D E W E C K , A . L . 8 . 3 , 8 . 7 W E C K E R , E . 12.8 W E I N G Ü R T E R , F . 10 .19 W E I S S , S. 35 W E K E R L E , H . 8.4, 8 .10 W E L T Z I E N , H . U . 4 9 8 W E N Z E L , B. Symp. 1 . 4 , 6 . 5 ,

8 . 1 8 , 1 2 . 2 6 W E N Z E L , K . W . 8 . 1 8 , 1 2 . 2 6 W E R N E T , P . 5 . 2 , 5 . 5 , 6 . 1 , 6 . 4 ,

6 . 6 , 1 2 . 1 8 W E S S E L S , F . 6.3 W E S T P H A L , E . 6 . 2 , 6 . 9

W l C K , G . 1 .7 ,2 .10 , 7 . 4 , 8 . 5 , 8 . 1 9 , 1 2 . 1 1 , 1 2 . 2 1 , 3 7 2

W I E D E R M A N N , G . 7.11 W I E D M A N N , K . H . 2.9 W I E S I N G E R , D . 454 W I L L E R S , J . M . 309 WiSSLER, J . H . 8 . 2 0 , 1 2 . 2 7 W ö L K - P ü S C H E L , I . Symp. 2 .4 W O L F , C H . 11.4 W O L F , H . 12.11 W O L F F , K . 11.14 W O L F F , M . H . 76 W O O D Y , J . N . 13 W O R S T , P . 12.29 W O T T G E , H . U . 12.28 WRABETZ, W . 11.9

W R A B E T Z - W Ö L K E , A . 11.2,

11.8

W R E M B E L , J . K.

4 2 9

Y E T E N O F , E . 10 .17

V O N Z A B E R N , J . 7 .13 Z A L E W S K I , P . D . 138 Z A W A T Z K Y , R. 3 . 3 , 3 . 7 , 6 5 Z E I L L E R , K . 4 . 7 , 4 . 8 Z I E G L E R , A . 5 . 2 , 5 . 5 Z I E G L E R , H . W . 10.5 Z I E L I N S K I , C H . 12.14 Z I E M E R , E . 11.1 Z I N K E R N A G E L , R. U . Symp.

2.1 Z i R M , U . 12 .30 Z O L L , A . 76 Z Ö L L E R , M . 1 0 . 2 0 , 4 8 3

Subject Index

Activation of T-lymphocytes, role of macrophages

Adverse drug reaction, complement . . Adverse drug reactions, acetylsalicylic

acid Alkyl-lysophospholipids, lymphocyte

response Alkyl-lysophospholipids, macrophage

activation Allogeneic bone marrow transplanta­

t ion, immune reactivity Allografted epidermal cells, survival . . Alloimmune disease, organ-specific . . Alloreactive and H-2-restricted Killer

cells, Generation Alloreactive cytotoxic T cells, stimulated

by viral Antigens Alloreactive cytotoxic T lympho­

cytes Alloreactivity, Hypothesis on the O r i ­

gin Anaphylactoid reactions, antibodies . . Antibody-dependent cell-mediated cy­

totoxicity ( A D C C ) , chronic active hepatitis ( A H )

Ant ibody dependent ki l l ing, cation re­quirement

Ant ibody responses, specific helper fac­tor

Antigen, oral application Antiglobulin test, radioactive Antimacrophage antibodies Anti-mucopolysaccharide (MPS), anti­

bodies Anti-murine B cells serum, specifici­

ty a , -Ant i t rypsin , Complement Recep­

tor Arthus reactions chemotactic factor

inactivator Ascites of tumor bearing mice, macro­

phage mediated tumor cytostalis . . Atopic dermatitis, suppressor cells . . Autoimmune reactions, induction . . . Autoimmune thyroiditis, effector

cells Autoimmunity , diabetes mellitus . . . Auto-reactive A-l ike determinant . . .

Basement membrane collagen, anti­bodies

Basement membrane collagen, immuno-509 histological studies 372 240 BCG-injected guinea pigs, hypersensi­

t iv i ty reaction 477 240 B-cells, anti-Serum 342

Bf polymorphism 237 498 Basic encephalitogeneic protein, charac­

terization 242 255 Basophilic leukemia (RBL), aggregated

IgGa 205 302 B lymphocyte differentiation, 303 chicken 186 250 B-lymphocyte mitogens, bacterial cell

surface components 213 96 B-lymphocytes membrane proteins . . 291

B-lymphocytes, stimulation of D N A -83 synthesis by anti-Ig antibodies . . . 209

Bone marrow cultures, colony types . 189 Bone marrow transplantation, cellular

immunocompetence 278 2 Bone marrow transplantation, immune-

289 endocrine network 179 Bullous pemphigoid, autoantibodies . 252 Bursectomy, chronic serum sickness . 185

210 C I q collagen-like helices 295

25 C3, lipopolysaccharides and l ipid A . . 441 Carcinoma, oral cavity and the tonsil . 268

13 Cardiac diseases, antisarcolemmal anti-289 bodies 280 197 Cation requirement, antibody depen-257 dent k i l l ing by human lymphocy­

tes 25 199 Cell mediated cytotoxicity (SCMC), re­

lationship to M L R 204 342 Chemotactic factor inactivator, Arthus

reactions 299 153 Chemotaxis, lymphocytes 301

Cholestatic liver disease, complement 299 f ix ing PBC 196

Cholestatic liver disease, trypsin insensi-267 tive subcellular antigen 195 284 Collagen, 1 4 C-collagen radioimmuno-248 assay 197

Collagen, juvenile rheumatoid arthri-244 tis 197 180 Collagen, type I and type I I 197 410 Complement activation of the alternative

pathway 239 Complement activation, k i l l ing of sal-

372 monella minnesota 234

568 • Subject Index

Complement cobra venom factors . . . 241 Complement components, purification

of human component C6 142 Complement consuming antibodies, p i ­

geon breeders' disease 523 Complement consuming IgG subclass

antibodies, pigeon breeders' dis­ease 168

Complement, interaction w i t h E. histolytica 240

Complement, interaction of D N A . . 236 Complement, membrane attack . . . . 238 Complement receptor, analogous factors

in Human Serum 153 Complement receptor, a ! - A n t i t r y p ­

sin 153 Combined immune deficiency syn­

drome 281 Contrast media, in vitro histamine re­

lease 194 Cortisol effects, suppressor cell activi­

ties 213 C T L , herpes virus specific 203 Cyclosporin A, mechanism of action . 454 Cytotoxic T cell, virus specific 83 Cytotoxic T lymphocytes, induction . 211 Cytotoxicity, effector lymphocytes . . 320

Delayed-type hypersensitivity, anti-tu­berculin antiserum 477

Diabetes mellitus, autoimmunity . . . 180 Diabetes mellitus, immune comple­

xes 283 Diabetes, transfer by lymphocytes . . 248 Diabetic patients, islet-cell antibodies . 246 Dialysable transfer factor, chemical

nature 353 Dialysable transfer factor, leukocyte dia-

lysate 353

Enzyme-immunoassay, quantitation of human Ig 193

Eosinophil chemotactic factor (ECF) generation 293

Essential hypertension, H L A - B 1 7 . . . 230

Graves disease, lymphokines 300 Group A-variant polysaccharide anti­

bodies, light chain heterogeneity . . 35 Growth factor (TCGF), suppressor

cell 220 G V H R , T-cell-mediated reactivity . . 251

H-2 Alloantigen, syngeneic anti-tumor serum 110

H - 2 restricted killer-cells, generation . 96 Helper factor, induction of antibody re­

sponses 13 Hepatitis B, antibody-dependent cell-

mediated cytotoxicity ( A D C C ) . . . 210 Herpes simplex virus, antigenic rela­

tionship to varicella-zoster virus . . 76 Herpes simplex type 2 (HSV2) infec­

tions, effector mechanisms 201 Histamine release, contrast media . . . 194 Histamine release, serum factors . . . . 209 H L A - D , - D R heterogeneity 296 H L A - D R serology, transplantation . . 231 H L A - D R w 3 , systemic lupus erythema­

tosus 232 Hodgkin's disease, immunoglobulin-se-

creting cells 273 Hodgkin's disease, lymphocyte reactivi­

ty 264 Hybridomas, monoclonal antibodies to

human group A erythrocytes . . . . 226 Hyperthermia, effect on lympho­

cytes 429

Ig , enzyme-immunoassay 193 IgE, antiidiotypic antibodies 243 IgE, antiidiotypic antiserum 245 IgE monoclonal gammopathy, «be­

nign» 280 I g M antibodies to rubella-virus and cy­

tomegalovirus, detection by Elisa-technique 192

I g M and IgA samples, quantitation by fluoroimmunometric technique . . . 192

Immune complexes, detection using Raji cells 191

Immune response, mother to the fe­tus 179

Immune complexes, R I A 194 Immune complexes, thyroid diseases . 198 Immune reactivity, T-cell mediated . . 207 Immune responses, genetic control . . 221 Immunocompetent T helper cells, corti­

cal thymocytes 201 Immunolatex, procedure for light and

fluorescence microscopy 138 Immunoregulatory function modula­

tion 282 Infections wi th group A-streptococci,

immunogenetic aspects 230 Inflammatory bowel disease, suppressor

cell activity 278 Insulin-dependent diabetics, TSH-re-

ceptor 231 Interferon production, herpes simplex

virus 202

Interferon production, M L C Interferon, producer cell in human l y m ­

phocyte cultures Interferons, N K and K cell activity . .

Keratitis disciformis Kidney diseases, immune complexes Kidney transplant patients, suppressor-

cells Kupffer cells, H-2 linked I r gene expres­

sion

Laser immunofluorescence, bleaching characteristics of F I T C conjugates

Laser-nephelometry, rheumatoid fac­tors

Lens permeability factors Leukemic cells, H L A antisera Leukocyte aggregation, complement-

derived peptides Lewis lung tumor, immunoprophy-

laxis Light chain heterogeneity Lipopolysaccharides, interaction w i t h

C3 Lipoprotein from Escherichia coli . . . Lipoprotein, mitogenicity Liposomes, kinin and complement . . Lymphocyte response, alkyl-lysophos-

pholipid Lymphocytes, stimulation by ribosomal

proteins Lymphoblastoid cell, lines, antibody

production against group A strepto­coccal carbohydrate

Lymphoblastoid cells, lectin binding sites

Lymphoblasts, proliferative response Lymphocyte cultures, producer cell of

interferon Lymphocyte plasma membranes, C a + + -

binding Lymphocyte transformation test, Graves

disease Lymphocytes, autokilling Lymphocytes subsets, glycoproteins Lymphoid cells, morphology and anti­

genic surface determinants Lymphoid tissue, localization of cell

markers Lymphocyte populations bone mar­

row Lymphokines, chemokinesis Lymphokines, Graves disease Lymphotoxin production

Subject Index • 569

202 L y t T cells subpopulations, generation of alloreactive and H - 2 restricted k i l -

65 ler cells 96 208

Macrophage activation, alkyl-lysophos­pholipids 255

Macrophage associated antigens, mono-clonal antibodies 227

Macrophage, generation of T effector 2 7 9 cells 183

Macrophage-mediated cytotoxic capaci-2^1 ties, fetal and neonatal mice 258

Macrophage mediated tumor cytostasis, ascites 267

196 Macrophage mediated cytotoxicity, anti­body-dependent and lymphokine-in-

193 duced 204 298 Macrophage migration inhibitory activi-233 ties, characterization 262

Macrophage, neuraminidase 256 234 Macrophage T cell interaction, I r

genes 262 269 Macrophages, anti-rat macrophages

35 sera 331 Macrophages, activation of T- lympho-

441 cytes 509 418 Macrophages, alveolar and peritoneal . 331 418 Macrophages, interferon inducers . . . 259 253 Macrophages, collagen type I I 239

Macrophages, complement system . . 239 498 Macrophages, Fc receptor 258

Macrophages, fibronectin 256 464 Macrophages, helper T cell induction . 263

Macrophages, lectin-like receptor . . . 259 Macrophages, plasminogen activator . 260

41 Macrophages, prostaglandin E, . . . . 260 Macrophages, Proteinase-treatment . . 255

288 Malignancies, monocyte mediated cyto-249 toxicity 272

Mast cell activation, IgE receptor . . . 206 65 Mast cell responses, evaluation . . . . 296

Mast cells, development 470 286 Mast cells, in vitro development . . . . 186

Mastocytoma, intradermally develop-252 ing 382 249 Mastocytoma, in vivo and in vitro i m -215 mune reactions 382

Melanoma associated antigens 274 188 Melanoma cell-line blocking effects . . 270

Melanoma cell, surface structures . . . 265 199 Melanoma, suppressor cells 271

Mistletoe extract, adjuvant activity . . 309 216 Mitogenicity of lipoprotein 418 301 Monoclonal antibodies, cell lines . . . 225 300 Monoclonal antibodies, cell surface anti-287 gens 224

570 • Subject Index

Monoclonal antibodies, controlled by the major histocompatibility com­plex 226

Monoclonal antibodies, immunoabsorp-tion of yeast catalase 223

Monoclonal antibodies, macrophage as­sociated antigens 227

Monoclonal antibodies, reactivity w i t h H 2 antigens 225

Monoclonal anti-idiotypes, diversity . 227 Mononuclear phagocytes, cytochemical

studies on the differentiation . . . . 187 M . Waldenstrom, anti-i autoantibod­

ies 281 Myasthenia gravis, suppressor cells . . 283 Myeloid precursor cells, bone mar­

row 189 Myeloma, idiotype bearing l y m p h o ­

cytes 273

Natural cytotoxicity in man 184 Natural killer cell activity, Crohn's dis­

ease 277 Natural killer cells, stimulation by C.

parvum 212 Natural killer cells, suppression by mac­

rophages 212 Natural ki l l ing ( N K ) , immunodeficiency

syndromes 206 Neutrophil-mediated cytotoxicity, ox i ­

dant generation 208 N K - and K-cell activity, trypsin-treat-

ment 211

Parasites, cell-mediated immunity . . . 182 Parasite-induced proliferative response,

T lymphocytes 205 Parasites, major transplantation anti­

gens 182 Parathyroid hormone (PTH), antibod­

ies 290 Pemphigus vulgaris, plasmapheresis . . 277 Phagocytosis, release of lysosomal en­

zymes 235 Phagocytosis, complement mediated . 237 Pigeon breeders' disease, complement

consuming antibodies 523 Pigeon breeders' disease, complement

consuming IgG subclass antibod­ies 168

Pineal function, endocrine network . . 179 Plaque-forming cell assay, chicken

system 236 Plasmapheresis, pemphigus vulgaris . . 277 Plasmocytoma, immune response . . . 266

Plasmodium knowlesi, specific anti­gens 297

Pregnancy, immunological dissection . 297 Pregnancy, prolactin 292 Proteolytic activity, tumor-membrane-

associated 274 Psoriasis, T-cell responses 229

Rheumatoid arthritis, B-cell alloanti-gens 232

Rheumatoid arthritis, genetic basis . . 229 Rheumatoid arthritis immune comple­

xes 284 Rheumatoid arthritis, immune

system 295 Rheumatoid arthritis, leukocyte loco­

motion 293 Rheumatoid factors, laser-nephelome-

try 193 Ribosomal proteins, stimulation of l y m ­

phocytes 464

Sandwich isotopic antiglobulin assay 483 Sclerosing panencephalitis (SSPE), l y m ­

phocyte function 191 Self recognition, B-cells and regulatory

T-cells 242 Self, recognition in aging 246 Sensitized individuals, immunopharma-

cological approaches 200 Serum amyloid A protein (SAA) . . . . 295 Specific Antibody Production against

Group A Streptococcal Carbohy­drate, Human Lympho-blastoid Cell Line 41

Spontaneous tumors, antitumor affector mechanisms 276

Spontaneous tumors, sandwich isotopic antiglobulin assay 483

Streptococcal M-protein, mitogenic properties 537

STH, metabolism in normal and nude mice 286

Suppressor factor, antigen specific . . . 400 Suppressor cell activities, Cortisol ef­

fects 213 Suppressor cell activity, carcinoma of

bladder and kidney 275 Suppressor cells, enrichment 218 Suppressor cells, myasthenia gravis . . 283 Suppressor cells, induction 400 Suppressor populations, identification in

human peripheral blood 215 Suppressor T-lymphocytes, bordetella

pertussis 218

Subject Index • 571

Sympathetic ophthalmia, immune reac­tions 292

Systemic Lupus erythematosus, H L A -DRw3 232

T-axis differentiation antigens, charac­terization 185

T G and T M cell subsets 219 T cell growth factor (TCGF), tumor pa­

tients 266 T-cell lines 364 T-cell populations, antigen-specific sec­

ondary T-lymphocytes 247 T cell reactions, N Z B mice 250 T-cell replacing factor (TRF) 290 T cells, cooperative induction 121 T cells, generation of virus specific cyto­

toxicity 83 T-cells, polyclonal specificity w i t h an

apparent anti-self component . . . . 121 T cells, Xenoserum-Induced 121 T cell subpopulations, surface protein

patterns 217 T cell subsets, generation of effector

cells 96 T C G T , suppressor cell mediated regula­

t ion 220 T effector cells, macrophages 183 T-helper function, chimeric mice . . . 203 Thymectomy, serum sickness 185 Thymocyte plasma membrane pro­

teins 300 Thymocyte surface antigen (HTA1) ,

leukaemic cells 223 Thymus-brain antigen 216 Thyro id antibodies, Ig-classes 198

T h y r o i d antibodies, various tests . . . 198 T h y r o i d diseases, thyroid antibodies 299 T h y r o i d stimulating, autoantibodies . 181 T-lymphocyte colony forming units,

agar micro culture 221 T-lymphocyte memory in vitro, induc­

t ion 243 T-lymphocyte proliferation, IA- l ike an­

tigens 245 T lymphocytes, alloreactive cyto­

toxic 207 T-lymphocytes, chicken antibodies . . 214 T lymphocytes precursors, develop­

ment 188 T M and modulated T G cells, immuno-

regulatory function 219 Transplantation, H L A - D R serology . 231 Trophoblastic cells, isolation 287 T - T cell cooperation, cytotoxic T l y m ­

phocytes 182 T stimulator cells, syngeneic M L R . . 220 Tumor antigens, expression 265 Tumor ascites, anti tumor affect . . . . 270 Tumor-bearing rats, lymphocyte sensiti­

zation 268 T u m o r growth, spleen size 271 T u m o r regression, routes of tumor cell

injection 264 Type-specific antibody to streptococcus

pyogenes, isolation 48

Varicella-Zoster virus, antigenic rela­tionship to Herpes Simplex Virus . . 76

Wheat-germ agglutinin, interaction w i t h streptococci 57

I m m u n o b i o l . , v o l . 156, p p . 83-95 (1979)

Institut für Immunologie und Genetik, Deutsches Krebsforschungszentrum, I m Neuenheimer Feld 280, 6900 Heidelberg, Federal Republic of Germany

Generation of Virus Specific Cytotoxic T Cells In Vitro, I I I . Spleen Cells Stimulated by Viral Antigens Generate Alloreactive Cytotoxic T Cells 1)

U . K O S Z I N O W S K I , D . GREBER, and I . N E U S C H A E F E R - R U B E

Received June 15, 1979 • Accepted June 25, 1979

Abstract

Cytotoxic T lymphocytes (CTL) f rom DBA/2 strain mice primed w i t h Sendai virus (SV) in vivo were activated by secondary stimulation of spleen cells w i t h viral antigens in vitro and analyzed for their target antigen specificity. These effector cells lysed syngeneic Sendai virus infected target cells, marginally a variety of non-infected targets and had a strong cytotoxic effect on H - 2 b targets. Studies on the antigenic requirements revealed that all SV preparations which generated specific C T L also induced the alloreactive populations. Similar results were found in the response to Newcastle disease virus ( N D V ) and some influenza A viruses; all these viruses were mitogenic for lymphocytes. Experiments on the cellular requirements indicated that virus specific and alloreactive cells can be separated by their requirements for help and for restimulation. By competition experiments both activities could be attributed to clearly separable T cell subpopulations. The induction mechanism of alloreactive T cells by viral antigens is discussed.

Introduction

H - 2 restricted cytotoxic T lymphocytes ( C T L ) are generally rather specific f o r the antigen and f o r the restrict ing H - 2 determinants. H o w e v e r , the d iscr iminatory capacity of these cytotoxic T cells is not absolute. Exceptions have been observed and fal l i n t o the f o l l o w i n g patterns: T N P -specific C T L have exquisite antigen specificity (1) but their specificity f o r the restrict ing H - 2 antigens is less p r o m i n e n t . O n the other hand, the H - 2 restr ict ion specificity of cytotoxic effector cells w i t h antigen specificity f o r viruses or m i n o r H-antigens is clearly demonstrable. T h e y do n o t lyse allogeneic target cells carrying the same vira l antigen (al though there is some crossreactivity between H - 2 k and H - 2 d ) and even have the capacity to differentiate between H - 2 mutants (2-4) . H o w e v e r , they show extensive crossreactivity o n target cells carry ing antigens of serological dist inct v i ra l substrains (5), they lyse syngeneic T N P m o d i f i e d target cells (6) and there is even cy to ly t i c act ivi ty o n allogeneic target cells w i t h o u t any m o d i f i c a t i o n b y virus or hapten (7, 8).

Abbreviations: CTL = cytotoxic T lymphocytes; GM = growth medium; NDV = Newcastle disease virus; SV = Sendai virus.

') Supported by the Deutsche Forschungsgemeinschaft Ko 571/5 and Ko 571/7

84 • U . K O S Z I N O W S K I , D . G R E B E R , and I . N E U S C H A E F E R - R U B E

Based o n the crossreactive patterns observed i t has been recently p r o ­posed that all alloreactive effector cells represent crossreactive cell popula ­tions w h i c h are generated i n the response to environmenta l antigens w h i c h elicit n o r m a l l y H - 2 restricted responses (9). I n this r e p o r t w e describe the generation of alloreactive T effector cells i n the response to three antigeni-cally unrelated viruses. Splenic lymphocytes f r o m D B A / 2 strain mice generate u p o n virus specific res t imulat ion i n v i t r o alloreactive cytotoxic T cells w h i c h lyse u n m o d i f i e d H - 2 b target cells. Studies o n the i n d u c t i o n mechanism and c o m p e t i t i o n experiments demonstrate that these effector cells represent separate subsets of C T L w i t h selective specif ic i ty f o r H - 2 K b

or H - 2 D b .

Materials and Methods

Animals: Mice from the strains DBA/2, BALB/c, B10.D2, B10.BR, C B A , B10.S, BIO, B10.A(2R), B10.A(5) and SWR were raised in our own breeding facility and used at 6-10 weeks of age.

Viruses: Sendai virus and influenza A/Victoria virus (H3N2) were propagated, titrated, purified and inactivated as described (10). Newcastle disease virus strain Italien ( N D V ) and the influenza virus strains APR/8 ( H O N 1 ) , A/USSR (H1N1) and A/ASIA ( H 2 N 2 ) were kindly supplied by Drs. Klenk and Rott, Gießen, ß-propiolactone inactivated Sendai virus (ß-pl-SV) (2 mg in 1 ml of the appropriate buffer) was digested w i t h proteolytic enzymes as described previously (11). Trypsin treatment (8 ul , 5 mg/ml; TPCK-treated, Worthington) was for 1 h at 37 °C in 0.5 % ammonium bicarbonate buffer, p H 8. Treatment w i t h V8 protease from Staphylococcus aureus: (50 ul , 1 mg/ml; Miles) for 18 h at 37 °C in 50 m M ammonium bicarbonate buffer p H 8. Sendai virus preparations were kindly provided by D r . M . J. Gething, ICRF, London, U K .

The capacity of the virus preparations to induce target cell formation was measured in the cytolytic assay (11, 12). Haemagglutinin, neuraminidase, haemolytic activities and cell fusion were tested as described previously. As reported in Reference 11 virus preparations treated with trypsin (TRY-SV) had haemagglutination and neuraminidase activities comparable to ß-pl-SV, but lacked the fusion capacity and the haemolytic activity (F"). The preparation digested wi th V8 protease from Staphylococcus aureus (V8-SA-SV) still contained the F glycoprotein but the haemagglutinin-neuraminidase glycoprotein spikes were removed from the virion ( H A N A - ) .

Immunizations: Mice were injected once i.p. w i t h 100 haemaglutination units ( H A U ) of infectious virus. 3-10 weeks afterwards spleens were removed and lymphocytes were prepared for tissue culture.

Media: Cells were cultured in RPMI1640 medium with L-glutamine (2 m M final concentra­tion) streptomycin and penicillin (50 units/ml), 2-mercaptoethanol (2 X 10"° M ) and 10% fetal calf serum.

Cell cultures: P-815 (H-2 d ) RBL5 (H-2 b ) and A K R A (H-2 k ) tumor cells were grown in vitro at a concentration of 2 X 105 cells/ml w i t h medium change after every 48 hrs. Mouse spleen cells or lymph node cells were suspended in medium at a concentration of 4 X 10 6 cells/ml. Cells were cultured in multi-dish culture trays (FB-24 Tc, Linbro Chemicals, N e w Haven, Conn., USA) or in plastic tissue culture flask of different sizes. If desired, cells were depleted from erythrocytes by lysis in 0.184 M N H 4 C 1 or by separation on a Ficoll-Hypaque gradient.

Growth medium: DBA/2 spleen cells (4 X 106/ml) were plated in mul t i dish trays and incubated for 48 hrs in the presence of 10 ,ug/ml concanavalin A (Pharmacia Uppsala, Sweden). After incubation the supernatant was harvested, centrifuged at 900 g for 10 min . , filtered through a 0.45 UJTI filter (Gelman, A n n Arbor , Mich . , USA) aliquoted and stored at -20 °C.

Alio reactivity Generated by Viral Antigens • 85

Growth medium was added to long term cultures in a 1:2 dilution with fresh complete medium. Cells in growth medium were seeded at a concentration of 2 X lOYml and were split when the cell concentration reached 0.5 X 106/ml or routinely after 4 days.

Helper cell culture conditions: Helper cells were generated by first step cultures in a modification of the protocol described by Baum and Pikrski (13). Helper cells were activated either specifically by viral antigens or alloantigens, or received no antigen. Helper cells obtained from a 1 day or 2 day first culture period were transferred into a second step culture to help a cytotoxic response by thymocyte killer precursors. Helper cells were irradiated with 1500 rad before addition to the thymocyte cultures. Controls included: 1. Thymocytes cocultured with irradiated helper cells in absence of viral antigens, 2. Irradiated helper cells in presence of viral antigens, 3. Thymocytes in presence of viral antigens in absence of helper cells. These controls were negative. Cytotoxic T cells were assayed at day 5 of the secondary culture.

5 1 Cr-release assay: The conditions of the 5'Cr-release assay and calculation of data are described in a previous paper (10). AH values are the mean percent specific MCr-release of triplicate wells. The standard errors of the means were always less than ± 5% and are omitted from figures and tables for clarity.

Results

Virus specific activated lymphocytes are cytotoxic for non-infected allogeneic target cells

Spleen cells f r o m D B A / 2 mice p r i m e d to Sendai virus were specifically rest imulated i n v i t r o and tested i n the 5 1 Cr-release assay o n various target cells (Fig . 1). D a t a show that a strong cytotoxic response was generated w h i c h c o u l d be demonstrated b y the lysis of Sendai virus infected syngeneic

D B A / 2 - S V

I T I I 20 10 5 2.b

D B A / 2 C3H BIO. A C 5 7 B I 6

\ P - 8 1 5 A K R - A

\ \

R B L - 5

K : T r a t i o

Fig. 1. DBA/2 spleen cells challenged with Sendai virus lyse non-infected allogeneic cells Responder cells are derived from DBA/2 strain mice primed with infectious virus 3 weeks previously. Targets are con A blast cells incubated with 10 ug SV antigen for 1 hr at 37 °C or tumor cells p-815 (H-2 d ) , A K R - A (H-2 k ) and R B L - 5 (H-2 b ) prepared similarly. Assay time 4 hrs.

86 • U . K O S Z I N O W S K I , D , G R E B E R , and I . N E U S C H A E F E R - R U B E

Table 1 . Generation of alloreactive cytolytic activity for H - 2 b targets by SV in different mouse strains

TARGETS Mouse strain 3) Haplotype % specific 5 1 Cr release*3)

syngeneic SV infected RBL-5 blast cells

DBA/2 H - 2 d 73 52 B 10.D2 H - 2 d 51 24 Balb/c H - 2 d 44 13 CBA H - 2 k 40 6 B 10.BR H - 2 k 47 9 B 10. H - 2 b 38 -2 B 10.S H - 2 S 35 3 SWR H-2*» 48 5

a ) Responders were primed in vitro wi th SV in vivo and restimulated in vitro wi th 1 ug/ml SV antigen.

b ) K : T ratio 20:1

con A blasts w h i l e non- infected syngeneic target cells were n o t lysed. W h e n tested o n semiallogeneic or allogeneic target cells various degrees of c y t o l y -sis were observed. W h i l e there was o n l y marginal lysis o n H - 2 k and H - 2 a

target cells H - 2 b blasts were lysed w i t h an efficiency comparable to the lysis of virus infected syngeneic target cells. T u m o r target cells of haplotype H -2 b o n l y were s imi lar ly lysed w h e n act ivi ty o n t u m o r cells of the haplotypes H - 2 d (P-815), H - 2 k ( A K R - A ) and H - 2 b (RBL-5 ) were compared. B o t h infected and non-infected H - 2 b target cells were lysed to the same extent (not shown) . I n c o n t r o l spleen cell cultures w i t h o u t Sendai virus antigens neither virus specific nor alloreactive cytotoxic act ivi ty was generated.

The capacity of Sendai virus to generate alloreactive cytotoxic act ivi ty was n o t restricted to the D B A / 2 strain mice. W h e n mice of the strains B10 .D2, B A L B / c , D B A / 2 , B10.BR, BIO and SWR were tested (Table 1), i t was f o u n d that in all H - 2 d strain mice some cytotoxic act ivi ty w i t h specificity f o r H - 2 b targets was generated w h i c h was n o t f o u n d i n the other strains tested. The cytotoxic act iv i ty on H - 2 b target cells could be abrogated b y the treatment of effector cells w i t h a n t i - T h y 1.2 serum and complement or a n t i - L y t 2.3 serum and complement indicat ing the T cell nature of the alloreactive cell p o p u l a t i o n (data n o t shown) .

Induction requirements of alloreactive cytolytic T cells following virus specific restim ulation

A ) Viral antigen requirements

D B A / 2 mice p r i m e d to an o r t h o m y x o v i r u s ( influenza A/Vic tor ia [ H 3 N 2 ] ) or paramyxoviruses (Sendai v i rus , Newcastle disease virus [ N D V ] ) were restimulated w i t h the sensitizing v i rus . I n the case of N D V and A / V i c t o r i a infective virus f r o m allantoic f l u i d was used as antigen. F o r

Alloreactivity Generated by Viral Antigens • 87

Sendai virus specific rest imulat ion i n this experiment, p u r i f i e d non-infec­tious virus was employed. A part of the SV preparat ion was treated w i t h t r y p s i n to destroy the funct ional act ivi ty of the fus ion p r o t e i n , w h i l e another preparation lacked the haemagglutinin-neuraminidase p r o t e i n , f o l ­l o w i n g V 8 protease treatment. The results of Figure 2 show that n o n ­infectious Sendai virus was also able to generate the alloreactive C T L p o p u l a t i o n and inact ivat ion of the F p r o t e i n or removal of the H N p r o t e i n was of l i t t l e effect. Fur thermore , i t is depicted that generation of N D V specific C T L was also accompanied b y generation of an H - 2 b specific act iv i ty , w h i l e an H 3 N 2 subtype of influenza A generated specific C T L w h i c h d i d n o t contain H - 2 b specific alloreactive cells.

Recently B U T C H K O et al. (14) reported that H 2 N 2 subtypes of influenza A viruses are mitogenic f o r lymphocytes . This effect could be a t t r ibuted to the haemagglutinin of type 2. Since i n our hands ( U . K . , unpubl ished) the glycoproteins of paramyxoviruses are also mitogenic f o r lymphocytes , we tested to see i f inf luenza A strains of H 2 N 2 subtype w o u l d also give rise to alloreactive C T L . F o u r influenza A strains d i f fe r ing w i t h respect to haemagglutinin and neuraminidase type were used f o r i n v i t r o p r i m i n g and f o r secondary s t imula t ion of C T L i n v i t r o . Effector cells were tested o n virus infected and non-infected target cells and i n addi t ion o n non-infected H - 2 b targets. As publ ished b y other authors (5) lysis of infected cells was specific f o r or thomyxoviruses b u t cross-reactive f o r the different influenza A subtypes (data n o t shown) . W h e n tested o n H - 2 b target cells (Table 2) o n l y , the H 2 N 2 subtype was active i n generation of alloreactive cy to ly t i c act iv i ty . H o w e v e r , to give rise to a s trong effect o n H - 2 b target cells i n v i v o p r i m i n g w i t h the H 2 N 2 subtype was required. A l s o , i n secondary st imula-

D B A / 2 S V p r i m e d B - p l - S V T R Y - S V S A - S V

D B A / 2 N D V p r i m e d D B A / 2 I N F L . p r i m N D V

P - 8 1 5 o P - 8 1 5 - S V O P - 8 1 5 - f I N F L , A ( H 3 N 2 )

P - 8 1 5 - I N F L . • R B L - 5

f f 20 10

K : T r a t i o

Fig. 2. Antigenic requirements for CTL activation R = responder cells; S = stimulator cells; T = target cells; N D V = Newcastle disease virus, strain Italien; I N F L = Influenza A virus, strain Victoria (H3N2) .

88 • U . K O S Z I N O W S K I , D . G R E B E R , and I . N E U S C H A E F E R - R U B E

Table 2. Lysis of RBL-5 ( H - 2 b ) tumor cells by influenza A virus specific activated DBA/2 spleen cells

Viruses used for in vivo Viruses used for restimulation in vi tro b ) priming 3 ) A/PR/8 A/USSR A/ASIA A / V I C T O R I A

A/PR/8 (HO N l ) 4.99 11.82 3.42 -2.96 A/USSR ( H I N l ) -2.38 5.79 7.43 1.40 A/ASIA (H2 N2) 12.80 13.70 82.91 29.37 A / V I C T O R I A (H3 N2) -1.26 0.68 -3.72 1.73

a ) DBA/2 mice were primed with 100 H A U infective virus containing allantoic f luid at least 3 weeks previous to secondary stimulation in vitro.

b ) Cytotoxic test on day 6 of in vitro culture; K : T ratio 10:1, incubation time 4 hrs

t i o n the other subtypes ( H 0 N 1 ) , ( N 1 N 1 ) and ( H 3 N 2 ) were active b u t the most effective response was again induced b y challenge w i t h the H 2 N 2 subtype. Thus , the experiments o n antigenic requirements f o r generation of the alloantigen-specific act ivi ty revealed that a) dif ferent mitogenic viruses and b) the same antigenic preparations of Sendai virus w h i c h give rise to H - 2 restricted k i l l e r cells w i l l also generate effector cells w h i c h lyse H - 2 b

target cells.

B) Cellular requirements

I n previous experiments we had f o u n d that virus specific cy totox ic effector cells could also be generated f r o m thymocytes i f antigen p r i m e d irradiated spleen cells were present i n the culture. For i n d u c t i o n of effector cells f r o m thymocytes the experimental p r o t o c o l described b y B A U M and P l L A R S K I (13) was applied. Three types of cell preparat ion w i t h helper cell f u n c t i o n were prepared: A ) D B A / 2 spleen cells st imulated w i t h Sendai virus , B) D B A / 2 spleen cells st imulated w i t h alloantigen (B10.BR, H - 2 k ) or C) D B A / 2 spleen cells w i t h o u t antigenic s t imula t ion . Cells f r o m type A , B or C were irradiated after 24 or 48 hrs i n tissue culture and 1 X 10 s of these helper cells were added to the cultures containing 1 X 10 8 thymocytes f r o m n o n - p r i m e d D B A / 2 mice and 1 (ig/ml Sendai virus antigen. The act ivi ty w h i c h was generated after 5 days of i n v i t r o culture was tested o n infected and non- infected syngeneic as w e l l as on allogeneic target cells. I t was f o u n d (Figure 3 A 1-3) that i n the presence of the irradiated cul tured cells A , B and C preincubated f o r 24 hrs, b o t h syngeneic virus specific act ivi ty and alloreactive act ivi ty was expressed. H o w e v e r , there was no c y t o l y t i c activ­i t y generated w i t h o u t helper cells present i n the culture (Figure 3 A , 4) and the effector cells were generated f r o m thymocytes and n o t f r o m the helper cell f rac t ion (Figure 3 A , 5). A f t e r preincubat ion of helper cells f o r 48 hrs previous to the addi t ion of thymocytes different results were obtained (Figure 3B). U n d e r these condit ions effector cell populat ions were obtained f r o m thymocytes w h i c h had alloreactive cy to ly t i c act ivi ty o n l y w h i l e there was no generation of virus specific effector cells. This indicates that the

Alloreactivity Generated by Viral Antigens • 89

R D B A / 2 T H Y M O C Y T E S — S V —

H A B C A T • P - 8 1 5 P - 8 1 5 - S V n I B L - 5

2 3 4

50-

(13 OO CO OS

as

20 10 5 2.5

K : T r a t i o Fig. 3. A H = helper cells, 1500 r irradiated 24 hrs preincubated; A = normal DBA/2 spleen cells preincubated with Sendai virus; B = normal DBA/2 spleen cells preincubated with B10.BR spleen cells; C = normal BBA/2 spleen cells preincubated without antigens added; 4 = no helper cells added to thymocyte responder cultures; 5 = no thymocytes added to helper cell cultures. B same helper cells incubated for 48 hrs

9 0 • U . K O S Z I N O W S K I , D . G R E B E R , and I . N E U S C H A E F E R - R U B E

generation of virus specific C T L and alloreactive C T L i n the presence of Sendai virus can be separated b y their di f ferent requirements f o r help. T i t r a t i o n experiments carried o u t i n order to define the quanti tat ive requirements f o r helper cells (data n o t shown) also indicated that the generation of alloreactive C T L required smaller numbers of helper cells.

H-2 restricted virus specific CTL and alloreactive CTL are different T cell clones

A) Competition assays

The results of the helper cell experiments already indicated that v irus specific and alloreactive cytotoxic act ivi ty reside i n dif ferent T cell subsets. B y compet i t ion experiments the specificity of the effector cells generated was evaluated. Sendai virus specific C T L f r o m the strain D B A / 2 were incubated w i t h 5 1 C r labelled SV infected con A blasts of the strain BIO ( H -2 b ) . The addi t ion of various non-labelled i n h i b i t o r cells (SV infected con A blasts of the strain B10 .D2 and non-infected con A blasts of the strains B10 .D2, B10.BR, BIO, B10 .A(2R) and B10.A(5R) showed that i n h i b i t i o n of lysis could o n l y be obtained b y addi t ion of compet i tor cells carry ing H - 2 b

antigens, w h i l e there was no i n h i b i t i o n of alloreactive k i l l e r act iv i ty b y addi t ion of n o r m a l or infected syngeneic cells or b y addi t ion of n o n -infected allogeneic cells of other haplotypes (Figure 4, 2). S imilar ly , w h e n tested o n 5 l C r labelled B10 .D2 blasts infected w i t h Sendai virus , o n l y H - 2 d

compet i tor cells infected w i t h Sendai virus were able to i n h i b i t the lysis of labelled target cells (Figure 4, 1). Thus , separate T cell subsets were

T : B 1 0 . D 2 - S V C 5 7 B I 1 0 B 1 0 A . [ 5 R ] B 1 0 A . [ 2 R ) i I

* 3

*

4

T 1 1 1 r -

0 5 1 0 2 0 4 0

R a t i o C o m p e t i t o r : T a r g e t s Fig. 4. Definition of effector cell specificity in competition experiments. Responder cells: DBA/2 spleen cells after secondary stimulation in vitro. Responder: target cell ratio 12.5:1. * no competitors added. Competitors (con A blasts): • B10.D2-SV O B10.D2, • B10.BR, O BIO, A B10.A (2R) ( K k , D b ) , V B10.A (5R) ( K b , D d ) .

Alloreactivity Generated by Viral Antigens • 91

generated i n the response to Sendai v i rus . O n e subset reacted o n l y w i t h syngeneic Sendai virus infected targets w h i l e the specificity of the other subsets was exclusively directed to H - 2 b alloantigens and d i d n o t cross-react w i t h antigens induced b y Sendai virus i n syngeneic cells. W e t r ied to map the target antigen(s) recognized b y the alloreactive C T L . The T cell subset w i t h al loreactivity f o r H - 2 b could be fur ther subdivided i n t o at least t w o clones, one very l i k e l y specific f o r H - 2 K b and the other f o r H - 2 D b as s h o w n b y fur ther c o m p e t i t i o n experiments (Figure 4,3, 4,4).

B) Long term culture conditions

L o n g t e r m tissue cultures (15-18) were set u p i n order to f i n d out i f b o t h populat ions have similar antigen rest imulat ion requirements. Cultures f r o m antigen p r i m e d mice were incubated w i t h Sendai virus i n order to generate virus specific effector cells. I n the same cultures cy to ly t i c activities specific for Sendai and f o r H - 2 b targets was generated. A f t e r 14-18 days i n v i t r o the cy to ly t i c act ivity o n b o t h targets started to cease. T o these cultures i r r a d i ­ated syngeneic s t imulator cells coated w i t h Sendai virus were added i n order to generate ter t iary cytotoxic effector cells. 6 days after rest imulat ion cytotoxic act ivi ty against syngeneic infected target cells could be d e m o n ­strated (Table 3, Exp . A ) w h i l e the c y t o l y t i c act ivi ty o n allogeneic target cells remained l o w ; yet, the potent ia l to generate alloreactive act ivi ty was not lost d u r i n g l o n g term culture. Cells f r o m cultures w h i c h previously had demonstrable c y t o l y t i c act ivi ty o n H - 2 b target cells were kept i n culture

Table 3. Effect of long term tissue culture conditions on alloreactive and virus-specific cytotoxic T cells

Exp. Day of in vitro1) Treatment of cultures K : T Target cells culture ratio (% 5 1 C r release)

P-815 P-815-SV R B L - 5

A 5 test 5:1 4 56 24 14 test 5:1 3 30 2 14 3° restimulation with SV

infected spleen cells 20 test 5:1 13 87 8

B 18 test 5:1 3 26 40 20 3°restimulation with SV

infected spleen cells 25 5:1 0 55 48 32 test and splitting of cultures 5:1 0 6 n.t. 35 test 5:1 0 0 2 32 transfer into growth medium 35 test 5:1 15 95 80

a) DBA/2 spleen cells challenged in vitro with Sendai virus. For restimulation cells were transferred into fresh complete medium. In Exp. B at day 32 cultures were split and 50% of the cells were transferred into medium supplied with con A induced growth medium.

92 • U . K o s z i N O W S K i , D. G R E B E R , and I. N E U S C H A E F E R - R U B E

u n t i l all cy to ly t i c act ivi ty had ceased (Table 3, Exp . B) . U p o n transfer i n t o tissue culture m e d i u m enriched w i t h g r o w t h m e d i u m w i t h o u t any a d d i ­t ional specific antigenic st imulus b o t h alloreactive and H-2-res tr ic ted v i rus specific c y t o l y t i c act ivi ty was restored. Therefore, the alloreactive T cells remained present under l o n g te rm culture condit ions a l though they were refractory to the antigenic st imulus b y Sendai virus m o d i f i e d s t imulator cells indicat ing different rest imulat ion requirements of b o t h cy to ly t i c T cell populat ions .

Discussion

Data show that paramyxoviruses and influenza virus strains of the H 2 N 2 subtype induce i n H - 2 d strain mice T effector cells w h i c h lyse syngeneic virus infected target cells and non-infected target cells carrying the haplotype H - 2 b . The alloreactive c y t o l y t i c act ivi ty can be induced w i t h infective inf luenza virus , Newcastle disease virus ( N D V ) and Sendai virus (SV). U s i n g SV non-infect ious virus preparations, v i r ions devoid of specific glycoproteins and vir ions carrying func t iona l ly inactivated glycoproteins were effective. These i n d u c t i o n condit ions are identical to that of v irus specific effector cells w h i c h recognize paramyxovirus antigens o n target cells ( t ) . Viruses w h i c h were able to generate al loreactivity had mitogenic effects o n lymphocytes .

The alloreactive cell p o p u l a t i o n w i t h c y t o l y t i c efficiency comparable to that of the virus specific H - 2 restricted effector cells resides i n a separate effector cell subset. This is revealed b y a) dif ferent antigen specificity i n co ld target cell i n h i b i t i o n tests b) di f ferent requirements f o r help d u r i n g i n d u c ­t i o n and c) dif ferent requirements f o r rest imulat ion under l o n g term i n v i t r o culture condit ions . Al together we report that alloreactive C T L w i t h o u t crossreactive cy to ly t i c act ivi ty o n virus infected target cells are generated f r o m spleen cells i n v i t r o u p o n antigenic s t imulat ion b y v ira l antigens.

I t has been s h o w n b y several authors that m u r i n e spleen cells st imulated b y antigens w h i c h induce a H - 2 restricted response contain C T L , w i t h specificity for the sensitizing antigens, but also addit ional effector p o p u l a ­tions w h i c h recognize unrelated antigenic determinants (5-9, 18). Since the specificity of the i m m u n e repertoire is l i k e l y to be defined b y various degrees of affinities rather than b y subsets of non-over lapping specificity some crossreactivity was to be expected. The T cell subsets w i t h addit ional reactivity described so far were defined b y c loning of effector cells (8, 18) or b y c o m p e t i t i o n studies w i t h non-label led target cells (6, 9). These studies revealed that those effector cells were crossreactive i.e. the same T cell clones seemed to carry receptors specific f o r the syngeneic antigen-expres-

( , ) K O S Z I N O W S K I , U . , and M . J . G E T H I N G . Generation of virus specific cytotoxic T cells in vitro. I I . Induction requirements w i t h functionally inactivated virus preparations (submitted for publication).

Alloreactivity Generated by Viral Antigens • 93

sing target cells as w e l l as f o r allogeneic targets. This indicates that molecules expressed o n allogeneic targets may have antigenic determinants w h i c h the virusspecific effector cell cannot discriminate f r o m determinants brought about b y the antigen specific m o d i f i c a t i o n of syngeneic target cells.

Does the interpretat ion that the i n d u c t i o n of the alloreactive T cell clones b y viruses is antigen specific and that some sharing of antigenic determi­nants must exist even w h e n the relatedness is n o t demonstrable at the effector cell stage also apply to our findings? O n e possibi l i ty may be that the a f f i n i t y f o r the shared determinants induced b y the virus is h i g h d u r i n g i n d u c t i o n and l o w at the effector cell level. This is indicated b y recent data of B A K E R et al. (18). The i r effector cell populat ions were induced against allogeneic cells but showed crossreactivity o n syngeneic target cells. C l o n ­i n g revealed effector cell clones of all three possible specificities: clones w i t h specificity f o r the alloantigen o n l y , crossreactivity cells and cells w i t h selective specificity f o r syngeneic cells. I f the crossreactive clones had arisen b y antigen specific i n d u c t i o n i t is u n l i k e l y that o n l y clones w i t h exquisite specificity f o r syngeneic determinants were induced b y non-antigens specific mechanism. Fur thermore , other authors have s h o w n i n activation protocols similar to ours (9) that Sendai virus can i n fact induce crossreac­tive effector cells w i t h specificity f o r alloantigens and also f o r v i ra l antigens o n target cells. W e cannot exclude that i n our cell cultures, also, some crossreactive act ivi ty m i g h t have arisen. I f so i t was too small to be detected b y the compet i t ion assays. H o w e v e r , i t is d i f f i c u l t to envisage h o w the three viruses w h i c h neither serologically n o r o n the T effector cell level show antigenic crossreactivity all share determinants w i t h H - 2 b .

A n o t h e r possibi l i ty w h i c h can be advanced to explain the generation of alloreactive clones i n virus specific T cell activation is the i n d u c t i o n of unrelated t h i r d par ty antigenic determinants b y virus . I n this case o n l y the immunogenic presentation of determinants is a feature specific f o r some viruses; not , however, the antigens themselves. The antigens may be derepressed endogenous vira l antigens (19, 20) or cell surface antigens (21-23). The failure of the rest imulat ion of the alloreactive clones b y virus i n the long te rm cultures could be explained b y such mechanisms. Cells capable of expressing relevant antigenic determinants or regulatory T cells required f o r rest imulat ion to that antigen may n o t be present under those condit ions.

Since a) the alloreactive effector cell p o p u l a t i o n does n o t show any a f f in i ty f o r determinants induced b y the sensitizing antigen w h i c h are recognizable b y virus specific effector cells and b) antigenically unrelated viruses give rise to similar effector cell populat ions , i t is l i k e l y that the lack of a f f in i ty at the effector cell level reflects i n d u c t i o n b y non-ant igen specific mechanisms. B E V A N et al. (24) observed that concanavalin A induced in spleen cells f r o m H - 2 d strain mice the generation of alloreactive effector cells w i t h specificity f o r H - 2 b . H o w e v e r , the p o l y c l o n a l act ivation generates T cells of 10-100 f o l d less act ivi ty than w e f i n d b y s t imulat ion w i t h v ira l

94 • U . K O S Z I N O W S K I , D . G R E B E R , and I . N E U S C H A E F E R - R U B E

antigens, a l though the mitogenic effect of paramyxoviruses is l o w . Inf luenza viruses of the subtype H 2 N 2 have been reported to have mitogenic activities (14), I n our experiments the very same subtype induces alloreactive cy to ly t i c act ivi ty . Thus , the pro l i f e ra t ion data can n o w be l inked f o r the f i rs t t ime w i t h a T cell f u n c t i o n . T h e effect differs , however , f r o m effector cells generated b y con A , since i n v i v o p r i m i n g and i n v i t r o rest imulat ion is required. I f the process of activation is n o t antigen specific i t is necessary to explain the strong response towards the H - 2 d target. Fur ther experiments are required to define i f there is a predominant activation of C T L precursors specific f o r H - 2 b or i f D B A / 2 mice have a h i g h frequency of precursor T cells f o r this alloantigen.

I t has been argued that al l alloreactive T cells are crossreactive cell populat ions induced b y environmental antigens (9). O u r data seem to extend these observations i n showing that v i ra l antigens can even induce effector cells w i t h selective specificity o n l y f o r the alloantigen. H o w e v e r , we feel that the capacity of some viruses to trigger alloreactive cell clones does not necessarily indicate that this effect accounts f o r the presence of the large number of alloreactive T cell precursors.

Acknowledgements

We thank Ms. URSULA R O H M A N N for the preparation of the manuscript.

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Dr. U . K O S Z I N O W S K I , Institut für Immunologie und Genetik, Deutsches Krebsforschungs­zentrum, I m Neuenheimer Feld 280, 6900 Heidelberg.