The role of T4+ and Ly-2+ cells in skin graft rejection in the mouse.

The role of the different T cell subsets (T4+ or Ly-2+) cells in the rejection of murine skin grafts was examined using the in vivo injection of monoclonal antibodies. The rat antimouse monoclonal antibodies used were shown to be active in vivo and to successfully deplete T4+ or Ly-2+ cells. H-2 mutant strains were used so that class I or class II MHC antigens could be studied in isolation; non-H-2 antigenic differences were also examined. The results were clear: (A) for class I antigens, Ly-2+ but not T4+ cells caused rejection; (B) for class II antigens, T4+ and Ly-2+ cells were both separately involved (additive studies indicated the unlikely involvement of Ly-2+T4+ cells); (C) for non-H-2 antigens, T4+ and not Ly-2+ cells were involved. In sensitized mice only anti-T4 antibodies caused any prolongation--for a class II difference. Our results relate strictly to phenotype and we have not measured cytotoxic or delayed-type hypersensitivity (DTH) (or IL-2 secretion) of cells in the graft causing rejection; nonetheless for class II antigens, anti-T4 treated mice had impaired in vivo DTH responses and the mediator of the DTH response to major histocompatibility complex (MHC) antigens is T4+; for class I antigens, DTH responses were not easily measured but mice with depleted DTH response were still able to reject grafts with a class I antigenic difference. The studies show that Ly-2+ cells, alone, can lead to graft rejection (for class I antigens) and T4+ cells alone (for non-H-2 antigens) can do the same. For class II antigens, T4+ cells are likely to influence the generation of Ly-2+ effector cells, although the precise mechanism is not clear. The studies therefore show that there is no special cell surface phenotype associated with graft rejection; rather the antigens presented dictate which cells are involved. How these cells function in the graft has yet to be demonstrated.