The induction of donor-specific transplantation tolerance in pancreas transplantation combined with spleen in rat

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Aim : To investigate the role of spleen and regulatory T cell for pancreas transplantation.Method : After induction of diabetes mellitus by streptozotocin, spleen and/or pancreaticoduodenal transplantation (S/PTx or PTx) into the peritoneal cavity was performed using a modification of Lee's method. Graft survival was compared in isograft (Lew to Lew), allograft (DA to Lew) and allograft with tacrolimus induction (1mg/kg/day for 4days) groups. The rate of CD25+CD4+ T cell and the Foxp3 expression in peripheral blood (PB), recipient spleen (RS) and donor spleen (DS) were examined using Flowcytometry and RT-PCR, respectively. The specimen was obtained from RS, DS, and graft pancreas for histological examination on day7.Results : Isotransplanted S/PTx (n=4) and PTx (n=4) were both survived longer than 100days. Both allotransplanted S/PTx (n=6) and PTx (n=6) without tacrolimus rejected the graft on 12.3±2.7d, 11.7±2.9d, respectively. S/PTx (n=6) with tacrolimus survived for 22.8±7.9d, and PTx (n=6) with tacrolimus survived for 13.5±3.7d (p=0.0069). Rejected S/PTx grafts (n=5) showed that 1)CD25+CD4+T cells were dominant in PB, RS and DS, 2) Donor derived CD25+CD4+T cells disappeared after 7days. Survived S/PTx grafts (n=5) showed that 1)donor CD25+CD4+T cells remained in PB, RS and DS over 7days, 2)the rate of Foxp3 expression was in both RS and DS on day7 compared with Rejected graft (p=0.028). There were more lymphocyte infiltration and reduction in white pulp in RS and DS.Conclusion : The pancreas graft survived longer by combined spleen transplantation and a short course of calcineurin inhibitor. Donor derived regulatory T cells (Foxp3 and CD25/4 cells) existing in both recipient and donor spleen would lead micro-chimerism and prolonged survival.