ALLOGENEIC AND XENOGENEIC ISLETS ARE REJECTED BY DIFFERENT AND SPECIFIC MECHANISMS - A STUDY IN RODENTS USING A MIXED ALLOGENEIC-XENOGENEICISLET TRANSPLANTATION MODEL

Indirect evidence suggests that islet allo-and xeno-graft rejections a re two qualitatively, and not simply quantitatively, different process es. This, however, has never been clearly shown and a direct in vivo c omparison of cell-mediated allo-and xeno-graft rejections has never be en made, Therefore, Lewis rats were transplanted with either Wistar-Fu rth rat islets or fetal porcine islet-like cell clusters (ICC) under t he kidney capsule. Other Lewis rats were transplanted with Wistar-Furt h rat islets and fetal porcine ICC, which were mixed together into one single graft. Animals were left untreated or were treated with cyclos porin A (CyA, 20 mg/kg b.w., p.,o.,) daily. Twelve days following tran splantation, islet allo-and xeno-graft survival was evaluated morpholo gically and any cellular infiltration into the grafts was characterize d immunohistochemically. In untreated animals, both allogeneic and xen ogeneic islets were destroyed by massive cellullar infiltration. The m ain infiltrating cells in islet allograft rejection were TCR alpha/bet a-positive T-cells. In contrast, the main infiltrating cells in islet xenograft rejection were EDI-and ED2-positive macrophages. In islet xe nograft rejection, only a few T-cells were: found. In islet allografts removed from rats treated with CyA, many morphologically intact rat i slets were found. Only a few infiltrating cells were detected and thes e were both ED1-positive macrophages and TCR alpha/beta-positive T-cel ls. In CyA-treated rats transplanted with porcine ICC, we noted a mass ive infiltration with ED1- and ED2-positive macrophages and TCR alpha/ beta-positive T-cells, similar to that observed in untreated animals. Na endocrine cells were present. In mixed allogeneic-xenogeneic islet grafts transplanted into CyA-treated rats, many morphologically intact rat islets were found, as evidenced by positive staining for rat MHC class I. However, no porcine ICC remained, The xenogeneic islets in th ese mixed grafts were destroyed, by massive cellular infiltration, sim ilar to that observed after transplantation of xenogeneic islets alone . Obviously, the xenogeneic islets in these mixed grafts were rejected by a cell-mediated process qualitatively different from that of cell- mediated allograft rejection.