seropositive donors demonstrates that they recognise theextracellular domain of both isoforms of the nativeprotein indicating that this response may participate indisease pathogenesis. We investigated this hypothesis inexperimental autoimmune encephalomyelitis using a panNF155/186 mouse mAb to mimic the human autoantibodyresponse. Passive transfer (i.p.) of mAb induced a rapidexacerbation of disease that was associated with acorresponding increase in acute axonal injury. Intriguingthis occurred in the absence of any concomitant increasein the local inflammatory response or demyelination.Immunofluorescence microscopy revealed that binding ofthe transferred neurofascin-specific antibody wasrestricted nodes of Ranvier where it co-localised withvoltage gated sodium channels. These results identifyNF186 as a primary target for neurofascin-specific auto-antibodies and indicate antibody-dependent effectormechanisms are involved in the pathogenesis of axonalinjury and loss in multiple sclerosis.

doi:10.1016/j.clim.2007.03.008

#3203- Innate ImmunologySunday, June 10

10:45 am−11:05 am

IL-23 is Required for Induction of an Innate ImmuneResponse to Citrobacter RodentiumDarrell O’Quinn, Postdoctoral Fellow, University ofAlabama, Department of Pathology, Birmingham, AL,Trenton Schoeb, Professor, University of Alabama,Department of Genetics, Birmingham, AL, Casey Weaver,Professor, University of Alabama, Department ofPathology, Birmingham, AL

We have previously shown that infection of IL-23-deficient mice with the enteric murine pathogen Citro-bacter rodentium results in complete mortality within 7-10days following inoculation despite the presence of CD4+ IL-17-competent cells. Using a mutant strain of biolumines-cent C. rodentium, we here demonstrate that colonizationof the cecum and mid- and distal colon of IL-23-deficientmice occurs earlier and in greater numbers than in IFNγ-,IFNγR-, IL-12-deficient, or wild-type controls. Histopatho-logical examination of the lesions in IL-23-deficient miceconfirms the presence of massive numbers of bacteriaattached to intestinal epithelial cells of the mid- and distalcolon, and multi-focal areas of ulcerative necrosis indicatea limited or absent inflammatory response. Analysis of C.rodentium colonization in IL-17R-/- mice reveal no sig-nificant differences from wild-type controls suggesting thatIL-23, not IL-17, may be critical for the maintenance ofinnate defenses in the distal colon.

doi:10.1016/j.clim.2007.03.009

OR.70 Intestinal Epithelial Cell Derived ThymicStromal Lymphopoeitin Controls DendriticCell Function and T Regulatory CellHomeostasisIliyan D. Iliev, PhD Student, European Institute ofOncology, Milan, Italy, Erika Mileti, Laboratory Assistant,European Institute of Oncology, Milan, Italy, MariaRescig, Group Leader, European Institute of Oncology,Milan, Italy

The mucosal immune system has developed mechanismsto tolerate beneficial microflora, but in the same time toinitiate immunity against invading pathogens. How thesemechanisms function is still not completely understood. Inour current study we investigated the possible role ofEpithelial Cells (EC) as a “tolerance keepers” in the gutdriving the development of non-inflammatory DendriticCells (DC) able to promote CD4+CD25+Foxp3+ T regulatorycells (Treg) development. We developed a co-culturesystem, in which EC (Caco2 or primary intestinal EC)supernatants were used to condition monocyte-derived DC.We found that in both, human and mice, EC-conditioned DCwere producing less inflammatory cytokines in response tobacterial stimuli and favored the development of function-ally active Treg. These tolerogenic DC were involved indriving Treg also in vivo in mice. Thymic stromallymphopoeitin (TSLP) produced by EC, together withadditional factors, was involved in this process since DCconditioned with supernatants from Caco2 cell line“silenced” for TSLP, were unable to expand Treg. Finally,mice immunized with Salmonella loaded EC-conditioned DCwere less resistant to lethal Salmonella dose than controlmice, confirming their tolerogenic potential in vivo.Therefore, intestinal EC released TSLP, can influence gutDC function and can control the homeostasis of peripheralTreg. We propose that failure in this mechanism canparticipate in the pathology of Inflammatory BowelDisease.

doi:10.1016/j.clim.2007.03.010

OR.71 Critical Role of IFNg in Allograft ToleranceMediated by Foxp3+CD4+CD25+ Regulatory T Cellsand the Production of Indoleamine 2, 3-dioxygenaseby Graft Endothelial CellsPamela Thebault, PhD, INSERM U643, Nantes, France,Michele Heslan, IE, INSERM U643, Nantes, France, ThomasCondamine, PhD, INSERM U643, Nantes, France, AbdelhadiSaoudi, CR1, INSERM U563, Toulouse, France, Marcello Hill,Postdoctoral Fellow, INSERM U643, Nantes, France, RegisJosien, CR1, INSERM U643, Nantes, France, Ignacio Anegon,DR2, INSERM U643, Nantes, France, Maria-Cristina Cuturi,DR2, INSERM U643, Nantes, France, Elise Chiffoleau, CR 2,INSERM U643, Nantes, France

Regulatory T Cells IISunday, June 102:45 pm−4:45 pm

S130 Abstracts