The roles of host and donor cells in the rejection of skin allografts by T cell‐deprived rats injected with syngeneic T cells

Abstract

Monoclonal antibodies that define rat T helper cells and cytotoxic T cell precursors were used to deplete thoracic duct lymphocytes of one or other of these subsets and the residual cells injected into syngeneic T cell‐deprived rats bearing skin allografts. The subsequent fate of the grafts was compared with that of grafts on rats injected with unfractionated donor cells. Removal of cytotoxic T cell precursors from the donor inoculum did not affect the ability of the injected cells to mediate destruction of the grafts whereas removal of T helper cells led to prolonged graft survival. Using monoclonal antibodies to label cryostat sections, the phenotypes of the cells infiltrating rejecting grafts and healthy grafts were also established. Seven days after grafting syngeneic or allogeneic skin on T cell‐deprived rats, all grafts were heavily infiltrated with Ia+ macrophages, but by 4 weeks this infiltrate had subsided and the grafts, whether syngeneic or allogeneic, were in perfect condition. At this time animals bearing grafts were injected with thoracic duct lymphocytes depleted of cytotoxic T cell precursors. Within 6 days of these cell transfers the allogeneic grafts, but not the syngeneic ones, were infiltrated with large numbers of mononuclear cells. Many of these cells were T cells, as judged by their expression of a pan T cell antigen, defined by the monoclonal antibody MRC OX‐19, and many were Ia' macrophages. In addition there was a very heavy infiltrate of cells labeled by the MRC OX‐8 monoclonal antibody which detects both rat cytotoxic T cells and natural killer cells. T cell‐deprived rats contained elevated numbers of nonspecific cytotoxic cells. Evidence was obtained that these cells were MRC OX‐8+. The possible role of these cells and of Ia+ macrophages in allograft rejection is discussed. As part of these studies the phenotypes of the cytotoxic T cell precursor and the cytotoxic effector cell were determined. It was shown that both cell types were indistinguishable, in terms of their reactivities with monoclonal anti‐rat T cell antibodies, from rat suppressor T cells.