Prolonged Islet Transplantation Survival In STZ Induced Diabetic Mice By Targeting CD45RB,CD154 And DSG

Background. Pancreatic islet transplantation has been advocated as a way of overcoming the shortage of human donor tissue for the treatment of type 1 diabetes, but clinical application in humans is still not feasible. New immunosuppressive strategies are needed to control inexorable rejection. Anli-CD45RB monoclonal antibody and anti-MRl monoclonal antibody can suppress T cell activation to prevent rejection of murine islet allografts in mono-therapy or combinative therapy and treatment of DSG effectively inhibit the growth of naive T cells to suppress immunoreaction.Methods. C57B/6 mice were induced diabetes via injection of streptozotocin and were transplanted with allogeneic (SD rat ) islets under the kidney capsule. Recipients were divided in to four groups. Control group was injected saline, only group was treated DSG alone, double group was treated anti-CD45RB mAb plus anti-MRl mAb and triple group was treated anti-CD45RB mAb, anti-MRl mAb and DSG in combination.Results. All untreated control mice lost islet function, becoming hyperglycemic within 13—17 days after islet transplantation. The treatment of DSG alone didn't significantly prolong islet survival and were terminated 17—27 days after transplantation. The treatment of anti-CD45RB mAb plus anti-MRl mAb siginificantly prolonged islet allografts, but two mice suffered from hyperglycemic on the 95th 99th days after islet transplantation. Synergistic therapy of anti-CD45RB mAb, anti-MRl mAb and DSG in combination dramatically augmented islet allograft (>99 days), and all recipients maintained natural glucose levels and weights. Conclusions. The treatment of anti-CD45RB mAb, anti-MRl mAb and DSG in combination significantly prolongs survival of islet transplantation.