RAT PANCREATIC-ISLET AND SKIN XENOGRAFT SURVIVAL IN CD4 AND CD8 KNOCKOUT MICE

The relative contributions of the CD4(+) and CD8(+) T cell subpopulati ons in xenotransplant rejection were studied using CD4 and CD8 knockou t (KO) mice. Wistar Furth (WF,RT1(a)) rat pancreatic islet or skin xen ografts were transplanted into either CD4 or CD8 KO recipients and com pared 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 mi ce 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. Thes e results suggest that CD4(+) cells are essential for mediating islet xenograft rejection. These data also suggest that the absence of eithe r CD4(+) or CD8(+) T cells is not sufficient to prevent rejection of s kin xenografts. (C) 1997 Academic Press Limited.