The roles of T cell subpopulations in allograft rejection

In principle, cell-mediated allograft rejection can be brought about by cytotoxic T cells or by a DTH-like reaction. The first part of this article reviews the relative importance of these two mechanisms in graft rejection and concludes that the bulk of evidence points to cytotoxic T cells as being of major importance. In the discussion an operational definition of DTH is adopted--namely a mechanism that mediates bystander killing and depends on the existence of a radiation-sensitive effector mechanism. The rejection of skin and organ allografts in mammals is T cell dependent and the demonstration that such rejection can occur in heavily-irradiated T cell reconstituted animals and in the absence of demonstrable bystander effects leads to the conclusion drawn. This is not to imply that concomitant DTH reactions may not augment the rejection process nor to deny the possibility that in special circumstances DTH reactions may play an essential part. In the second part of this article, the roles in graft rejection of CD4+ and CD8+ cytotoxic T cells are considered. The classical collaborative interaction between class II-restricted CD4+ cells that play an inductive role, and class I restricted CD8+ cells that differentiate into cytotoxic effector cells, seems to be unnecessary in some allograft responses. Thus, not only can CD4+ T cells differentiate into class II-restricted cytotoxic T cells but CD8+ T cells, at least in some class I MHC-incompatible strain combinations, can develop into mature effector cells without an inductive signal from CD4+ T cells. This autonomy seems to be limited to MHC incompatibilities so that CD8+ cells alone are unable to mediate the rejection of minor-H incompatible grafts. For these latter types of grafts, CD4+ T cells can bring about graft rejection if multiple minor-H determinants are present, but for weak minor-H responses the classical collaborative scheme is necessary.