bone marrow t-cell infiltrates in viral infections and ... · bone marrow t-cell infiltrates in...

Bone marrow T-cell infiltrates in viral

infections and autoimmune diseases

Alexander Tzankov

Institute of Pathology, University Hospital Basel

Bone marrow T-cell infiltrates

• Physiological roles of mature bone marrow T-cells

• Bone marrow T-cells in viral infections

• Bone marrow T-cells in (auto)immune conditions

• Bone marrow T-cells and drug reactions

• Paraneoplastic bone marrow T-cell expansions

• Summary

Bone marrow T-cells, physiology

http://www.immunopaedia.org.za


• 7-9% B-cells

• 20-25% T-cells

8-9% CD4+ T-cells

14-18% CD8+ T-cells

CD4/CD8 = 0.5-0.7

2-5% NK-cells

• Higher & less CD8-skewed in aspirates

Clark et al. Blood 1986;67:1660


Dean et al. Immunol Let 2005;99:94

Di Rosa. Immunol Cell Biol 2009;87:20

• >50% of bone marrow T-cells express

CD69, early activation marker

HLA-DR, late activation marker

• Only 25% CD45RA+/RO- naïve T-cells

• Major source of CD8+ long-lived memory T-cells

• Region-specific regulative/protective function?


Herndler-Brandstetter et al. J Leuk Biol 2012;91:197

Herndler-Brandstetter et al. J Immunol 2011;186;6965

Feuerer et al. Nat Med 2003;9:1151

• Bone marrow T-cells stimulated in situ by dendritic cells

• Cytotoxic defense against systemic blood-borne antigens


Lord et al. Blood 1973; 42:395

Trainin et al. Nature 1969;221:1154

Ilstad et al. J Immunol 1984;136:28

Monteiro et al. Blood 2005; 15:105

Lee et al. J Immunol 2009;10:6377

Schwarzenberger et al. J Immunol 2000;164:4783

• Thymectomized mice become anemic

• T-cell infusion aid hematopoietic reconstitution

• Attributable to CD4+ bone marrow T-cells

• Dependent on MHC matching

• Major source of GM-CSF, IL3-6 & 13

• Granulopoiesis Th17/Treg dependent


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T-cells in pathological conditions








• Summary

Epstein-Barr virus

• Atypical peripheral T-cell lymphocytosis (CD8 skewed)

• Bone marrow T-cell lymphocytosis (CD8 skewed)

Occasional antigenic loss for CD5 or CD7

Occasionally T-cell clonality

• Plasmacytosis (more prominent in immunocompromized)

• PTLD

• Hemophagocytosis/Hemophagocytic syndrome

Epstein-Barr virus

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CD8

Early PTLD

EBER CD138

CD8

NK/TCL

CD3

EBER

Cytomegalovirus

• (T-LGL) atypical peripheral lymphocytosis

Occasionally T-cell clonality

• Bone marrow T-cell lymphocytosis (CD8 skewed)

• Fibrin ring granulomas

• Hypoplasia in immunocompromized

Cytomegalovirus

CD3

CD3

CD8

Human herpes virus 8

• Lympho-follicular hyperplasia

Occasionally with Castleman features

• Plasmacytosis

• T-cell increase

Bacon et al. Br J Haematol 2005; 127:585


LANA-1


CD3

LANA-1







• Summary

Marrow T-cells and autoimmunity

• T-cell (T-LGL skewed) lymphocytosis

• Erythro- and megakaryopoietic changes

Hemolysis (AIHA) & peripheral platelet consumption

“Anemia of chronic disease”

• Plasmacytosis

• (Autoimmune) myelofibrosis

• Pure red cell aplasia

• Aplastic anemia

Rizzi et al. Leuk & Lymphoma 2004;45:561

Bass et al. AJCP 2001;116:211

Voulgarelis et al. Am J Hematol 2006;81:590

Prochorec-Sobieszek et al. Arthritis Res Ther 2008;10:R55

Felty syndrome

Arthritis Res Ther 2008;10:R55

CD57 GrB

CD8 CD3

Marrow T-cells and autoimmunity

AJCP 2001;116:211 Leuk & Lymphoma 2004;45:561

k/l CD57

Aplastic anemia as a collateral

damage of immunosurveillance?

Maciejewski et al. Folia Histochem Cytobiol 2007;45:5







• Summary

Marrow T-cells and drug reactions

• Drugs commonly associated with T-cell increase Allopurinol

Phenytoin

Rituximab (Alemtuzumab)

Imatinib

HBV immunization

• Histopathology T-cell infiltration

Occasionally clonal

CD4 skewed, occasionally PD-1 increase

Eosinophilia

Myelopoietic maturation arrest

Granulomas

Villard et al. Br J Haematol 2000;110:230

Braziel et al. Blood 2002;100:435

Raynaud et al. Hum Pathol 2008;39:194

Johns et al. MJHID 2010;6207

Marrow T-cells and drug reactions

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Allopurinol induced DRESS

CD3 PD-1

PAS

T-cell expansion after Phenytoin

CD3

CD4 CD8

PAS

T-cell aggregates after Rituximab

CD3







• Summary

Paraneoplastic T-cell expansions

• B-cell lymphomas

Marginal zone B-cell lymphoma

Lymphoplasmacytic lymphoma

Follicular lymphoma

• AML, particularly MLL rearranged

• MDS

• MPN

• Thymomas

• Systemic mastocytosis

Horny et al. J Clin Pathol 2003;56:575

Magalhães et al. Leuk Res 2002;26:525

Smith et al. AJCP 1994;102:447

Cervantes et al. Br J Haematol 1988;70:279

Accompanying T-cells in MZL

CD5 CD20

Accompanying T-cells in AML M5A

CD3 CD11c







• Summary

Summary

• Important physiological role of T-cells in the bone marrow

• Rise and CD8 skewing in viral and autoimmune diseases

Look for viropathic effects and ask for clinics, serology & PCR

• Rise and CD4 skewing in adverse drug reactions

Ask for

• Attack, mask or accompany neoplastic diseases

Look for

bone marrow t-cell infiltrates in viral infections and ... · bone marrow t-cell infiltrates in...

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