Retransplantation of discordant xenogeneic islets with costimulatory blockade

BACKGROUND: The aim of the study was to analyze the possibility of xenogeneic islet retransplantation using costimulatory blockade. METHODS: Streptozotocin-induced diabetic mice were transplanted under the kidney capsule with human islets. Mice were nephrectomized and retransplanted with 1000 human islets under the contralateral kidney capsule 14 days later. Four groups were performed group I, first and second Tx without MR1; group II, first Tx without MR1, second Tx with MR1; group III, first Tx with MR1, second Tx without MR1; group IV, first and second Tx with MR1. A control group was transplanted only once without MR1 with human islets. After second Tx, cross-matches between recipient, serum and human lymphocyte were done for detection of antidonor antibodies. RESULTS: In the control group, mean graft survival was 13 (+/-7) days. In group I, mean graft survival was 5 +/- 3 days. In group II, mean graft survival was 16 +/- 13 days. In group III, mean graft survival was 81 +/- 22 days. In group IV, no rejection were recorded and all graft survived more than 120 days. Pretransplant cross-matches were negative. In groups I and II all cross-matches were positive, while none were positive in group IV. CONCLUSION: Retransplantation of xenogeneic islets was associated with accelerated rejection. After presensitization, MR1 was unable to induce tolerance to a second Tx. MR1 given at the first Tx only allowed prolonged survival of the second Tx, but rejection still occurred. MR1 given at first and second Tx allowed long-term survival of retransplanted xenoislets and prevented occurrence of antidonor antibodies.