we investigated two Th2 T-cell clones, 6.9 Tg.C6/T2 and 2.5 Tg/T2-X, which were derived from NOD T-cell receptor transgenic (TCR-Tg) mice. Both clones express the Th2 cytokines, IL-4, IL-5, IL-6, IL-10 and the regulatory cytokine TGF-h1, at both the gene and protein levels. These Th2 T-cell clones also express the regulatory T-cell marker, Foxp3, by RT- PCR and by western blot. In vitro the Th2 T-cell clones can inhibit IFN-g production by pathogenic Th1 T-cell clones and nitric oxide production by macrophages. Despite their inhib- itory properties in vitro, these two Th2 T-cell clones are pathogenic in vivo when transferred into young NOD- but not in NOD.scid-mice. Intracellular staining revealed that the Th2 T- cell clones produce low levels of TNFa , and in vivo, they migrate to the pancreas upon adoptive transfer to NOD.scid mice and express cytokines similar to those observed in vitro. We hypothesize that the TNFa produced by these Th2 T-cell clones contributes to their ability to cause diabetes. Supported by grants from NIH (RO1 DK50561) and JDRF (1-2004-49). doi:10.1016/j.clim.2006.04.468 Su.42. Modulation of Inducible Type 1 Diabetes By CD137 Costimulation. Govindarajan Rajagopalan, 1 Yogish Kudva, 2 Moon Sen, 1 Chella David. 11 Department of Immunology, Mayo Clinic, Rochester, MN; 2 Division of Endocrinology, Mayo Clinic, Rochester, MN. Rationale: In the spontaneous non-obese diabetic (NOD) mouse model of Type 1 diabetes, idd9.3 locus containing the CD137 gene shows strong genetic association. Structural varia- tion between diabetes-susceptible (NOD-derived) and the dia- betes-resistant (C57Bl/10-derived) CD137 molecules has been reported. Since CD137 is an important costimulatory molecule for CD4+ and CD8+ T-cells and costimulation through CD137 has been shown to prevent or ameliorate certain experimental autoimmune diseases, we investigated the therapeutic role of an agonistic anti-CD137 antibody (clone 2A, gift from Dr. Lieping Chen, Baltimore, MD) on two inducible models of T1D in NOD mice. Methodology: Purified rat anti-mouse CD137 agonistic antibody (2A) and its rat isotype control (IC) were used in this study. For adoptive transfer, 50 million splenocytes from recently onset diabetic female mice were transferred to sub- lethally irradiated (600R, day-1) female recipients on day 0, followed by 200 Ag of 2A or IC on days 0 and 7. For high-dose cyclophosphamide-induced diabetes model, 9—12 weeks-old non-diabetic female mice were challenged with 200 mg/kg cyclophosphamide (Cy) followed by 200 Ag of 2A or IC on days 0 and 7. The glycemic status was monitored weekly thereafter. Results: In the adoptive transfer model, 100% (4/4) of mice treated with anti-CD137 and 75% (3/4) of mice treated with isotype control became diabetic within 5 weeks of cell transfer. In the high-dose cyclophosphamide model, 50% (6/12) of mice treated with anti-CD137 and 55% (5/9) of mice treated with isotype control became diabetic in the 10 week follow-up. Conclusions: Administration of agonistic anti-CD137 monoclo- nal antibody does not confer significant protection against the incidence of inducible diabetes in NOD mice. doi:10.1016/j.clim.2006.04.469 Immunity and Infection Su.43. Compartmentalized Modifications of the Peripheral T-Cell Repertoire Are Associated to Experimental Cerebral Malaria. Encarnita Ferrandiz, Pierre-Andre Cazenave, Sylviane Pied, Adrien Six. Immunology, Institut Pasteur, URA 1961 CNRS and Universite Pierre et Marie Curie-Paris6, Paris, France. Cerebral Malaria (CM), one of the severe complications of Plasmodium falciparum infection, is responsible annually for 30% of the one million malaria related death worldwide. Moreover, children under five years of age and pregnant women are principal victims of the fatal outcome of this infection. In murine models of CM, Tah cells have been implicated in the neuropathogenesis. We carried out high throughput CDR3 spectratyping using the ISEApeaks strate- gy, developed in our laboratory, to get insights into the TCRBV repertoire during CM. We have previously observed that B10.D2 mice infected by P. berghei ANKA clone 1.49 (PbA) developing CM (CM+) present an altered PBL reper- toire, partly due to recurrently expanded T-cell clones, when compared to non-infected control mice but also to infected mice that do not develop CM. In order to evidence the dynamics of this alteration, we performed a kinetic analysis of TCRBV repertoire in PbA-infected mice, from day 3 post-infection (p-i) until CM-related death. The repertoire of PBL, splenocytes and brain lymphocytes was compared between infected and non-infected mice. Using the ISEA- peaks strategy, we could characterize the change of repertoire diversity during the course of infection. In comparison to non-infected mice, five BV appear to be significantly perturbed in the brain of infected mice and present an increased perturbation in blood and spleen during the course of infection and in CM+ mice. This alteration is detectable on the fifth day p-i in splenocytes, on the sixth day p-i in PBL and brain lymphocytes. These results provide evidence for a dynamic modification and compartmentalization of the T-cell repertoire diversity during the course of PbA infection. We are now character- izing the nature of the alteration of brain lymphocytes, in order to determine their role in the outcome of the cerebral syndrome. doi:10.1016/j.clim.2006.04.470 Su.44. Enhanced Proliferation and Hematopoiesis in Ly49q-Deficient Mice. Marie-Line Goulet, 1 Nassima Fodil, 2 Angela D. Troke, 1 Noriko Toyama-Sorimachi, 3 Etienne Rousselle, 1 Silvia M. Vidal, 2 Andrew P. Makrigiannis. 11 Laboratory of Molecular Immunology, Institut de Recherches Cliniques de Montreal, Montreal, QC, Canada; 2 Human Genetics, McGill University, Montreal, QC, Canada; 3 Gastroenterology, International Medical Center of Japan, Tokyo, Japan. Ly49s are members of a family of cell surface receptors expressed mainly on NK cells that have the ability to Abstracts S174