A more persistent tolerance to islet allografts through bone marrow transplantation in minimal nonmyleoablative conditioning therapy

Introduction. Islet transplantation is a therapeutic approach to prevent diabetes complications. However, the side effects of the required lifelong immunosuppressive regimens to prevent graft rejection restrict the impact of type 1 diabetes. One strategy to overcome these limitations is tolerance induction and graft acceptance through hematopoietic chimerism. In this study we investigated whether tolerance to major histocompability complex (MHC) and minor-disparate islet allografts could be induced by minimal nonmyeloablative conditioning and whether more persistent donor-specific islet allografts were accepted if the grafts were implanted with simultaneous bone marrow cells. Methods. The donor and recipient mice were BALB/c(H-2^b) and C57BL/6(H-2^d), respectively. In group 1 streptozotocin-induced diabetic C57BL/6(H-2^d) mice received only 500 islets of BALB/c(H-2^b). Group 2 recipients conditioned with antilymphocyte serum, 100 cGy total body irradiation and cyclophosphamide were given islet cells of BALB/c(H-2^b), but group 3 were simultaneously given 30 × 10⁶ BALB/c(H-2^b) mice BMCs and islet cells similar to group 2. Results. We obtained 5% to 6% allogeneic donor chimerism and 60% graft survival at 80 days after islet transplantation in group 3. We observed lymphocyte infiltration around the islet without destruction of endocrine cells and the presence of strong insulin/glucagon-stained cells in group 3. Conclusion. This minimal nonmyeloablative conditioning therapy induced donor chimerism and immune tolerance between MHC- and minor-disparate (BALB/c→C57BL/6) mice and long-term islet graft survival was obtained through cotransplantation of bone marrow cells.