CD8+T cells are capable of rejecting pancreatic islet xenografts

Background. In this study, the capacity of CD8+ T cells to act as a potenti al effector mechanism in pancreatic xenograft rejection was examined. Methods. The fate of pancreatic islet xenografts was studied in mice defici ent in MHC class II molecules and CD4+ T cells. Fetal pig pancreas (FPP) or Wistar rat islets (RI) mere transplanted into nondiabetic or streptozotoci n-induced diabetic I-A knock-out (CII K/O) mice. Results. CII K/O mice were capable of rejecting both RI and FPP grafts. RI graft survival was not prolonged compared with mild type C57BL/6 controls. However, FPP grafts did survive longer in CII K/O recipients than in C57BL/ 6 mice. Both RI and FPP graft rejection were CD8+ T-cell phenomena in CII K /O mice, as anti-CD8 monoclonal antibody prolonged graft survival, there we re increased CD8+ T cells in the grafts and spleens of CII K/O recipients, and cell-mediated cytotoxicity was a CD8+ T-cell phenomenon associated with activation of the perforin/granzyme B system. By contrast, RI and FPP graf t rejection was a CD4+ T cell-dependent phenomenon in wild type C57BL/6 mic e with graft survival prolonged by anti-CD4 monoclonal antibody. There were increased numbers of CD4+ T cells, and cell-mediated cytotoxicity was a CB 4+ T-cell phenomenon associated with activation of the Fas/FasL lytic pathw ay. Conclusions. The results demonstrate that, in the absence of CD4+ T cells, CD8+ T cells were capable of rejecting both rat and pig pancreatic islet xe nografts.