Roles of CD4+ and CD8+ cells in islet allo- and xeno-graft rejection.

We investigated the requirement for and the roles of CD8+ cells and CD4+ cells for islet graft rejection in allogeneic and xenogeneic combinations by in vivo administration of anti-Lyt2 monoclonal antibody (mAb), anti-L3T4 mAb or both to the recipient mice. In BALB/c to B6 (H-2 and non-H-2 incompatible combination), administration of anti-Lyt-2.2(CD8) or anti-L3T4(CD4) mAb resulted in rejection of most of the grafts, although their survival was prolonged significantly. Administration of both mAbs together completely blocked rejection and all allografts survived over 100 days with mAb administration. In B10.A(5R) to B10.A (H-2K and IA incompatible combination) or B10.AQR to B10.A (H-2K incompatible combination), administration of either mAb alone induced indefinite allograft survival. In bm12 to B6 (IA incompatible combination), allografts were not rejected even in nontreated recipients. In rat-to-mouse combinations, administration of anti-L3T4 mAb produced marked prolongation of graft survival and 3 out of 8 survived over 100 days. Administration of both mAbs also led to prolongation of graft survival which was similar to or better than that of anti-L3T4 mAb alone. The present results indicated that CD4+ and CD8+ cells participate in all types of islet graft rejection studied here and that the absolute requirements of CD4+ or CD8+ T cell subsets for islet rejection depend on genetic as well as species disparity.