Rat pancreatic islet and skin xenograft survival in CD4 and CD8 knockout mice

The relative contributions of the CD4+ and CD8+ T cell subpopulations in xenotransplant rejection were studied using CD4 and CD8 knockout (KO) mice. Wistar Furth (WF, RT1a) rat pancreatic islet or skin xenografts were transplanted into either CD4 or CD8 KO recipients and compared to wild-type controls. Long-term survival of WF islet xenografts was observed in the CD4 KO mice (MST, >66+/-8 days) whereas CD8 KO mice rejected their islet xenografts within 8 days, similar to controls (MST, 7+/-0.2 days). In contrast, WF skin xenografts were rejected in both CD4 and CD8 KO recipients within 8 days. CD4 KO recipients which maintained xenoislets >90 days posttransplant rejected WF skin grafts within 9 days, without rejecting their original islet xenografts. These results suggest that CD4+ cells are essential for mediating islet xenograft rejection. These data also suggest that the absence of either CD4+ or CD8+ T cells is not sufficient to prevent rejection of skin xenografts.