Immunomodulatory Cell Induction for Tolerance after Pancreatic Islet Transplantation

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Background: Pancreatic islet transplant (PITx) is a promising treatment optionfor patients with type 1 diabetes mellitus. We have previously induced tolerance afterliver transplantation by adoptive transfer of donor-antigen specific immunomodulatorycells (IMCs), where 70% of patients were successfully weaned off immunosuppressants. Wehypothesize that the same beneficial effects could be applied to PITx. Methods: IMCs were induced by co-culturing of C57BL/6 (H-2^b) mouse splenocytes with irradiated BALB/c (H-2^d) splenocytes in the presence of anti-CD80/86 monoclonal antibodies. The immunosuppressive effects were evaluated by MLR. LPS-activated RAW264 macrophages were cultured with IMCs to evaluate the anti-inflammatory potential. Results: IMCs suppressed the proliferation of C57BL/6 responder cells cultured with BALB/c stimulator cells in MLR. The addition of IMCs suppressed M1 marker expression and increased M2 markers. IMCs could be successfully injected into the liver in a mouse allogeneic PITx model. Conclusion: IMCs showed immunosuppressive and anti-inflammatory effects and could be safely injected in mouse PITx model.