Cells mediating graft rejection in the mouse. I. Lyt-1 cells mediate skin graft rejection

Abstract

It is commonly accepted that the in vitro lysis of allogeneic target cells by primed cytotoxic T cells (Tc)1 is an appropriate model for studying graft rejection. For example, Tc can be found in grafts undergoing rejection (1-3), in the spleen and other tissues of primed mice (1,4,5), and in sponge matrix grafts (6,7) In addition, extensive in vitro studies have demonstrated the induction and function of Tc, the requirement of helper T cells (Th) for their induction, and the simultaneous induction of suppressor T cells (5, 8-14). In these studies, it has become abundantly clear that the Lyt-123/23-Tc2 is different from Th cells (which are Lyt-1), suppressor T cells, and other T cells. In spite of the many experiments that support the concept that Tc produce graft rejection in vivo, there is little direct evidence demonstrating this, and most of the foregoing evidence can be regarded as 'indirect'. Indeed, it has not been clearly demonstrated that Tc have the only role, a major role, or any role in graft rejection in vivo. With this in mind, adult, thymectomized, lethally irradiated, bone marrow-restored (ATXBM) mice were repopulated with sensitized cells, depleted of Lyt-1, Lyt-2, or Lyt-123 subpopulations, and were then examined for the phenotype of the T cell causing skin graft rejection. With antigenic differences arising from the H-2 and non-H-2 loci, it was shown that graft rejection was entirely dependent on the presence of Lyt-1 cells and, furthermore, was independent of the presence of Tc. It appears that traditional concepts, linking graft rejection and delayed-type hypersensitivity (DTH), may well be true, in that both are mediated by Lyt-1 cells.