Suppression of cell-mediated lymphocytotoxicity against minor histocompatibility antigens mediated by Lyt-1+Lyt-2+ T cells of stimulator-strain origin

Abstract

Cultured, unprimed spleen cells suppress the generation of cytolytic T lymphocytes when added to mixed lymphocyte culture of cells disparate at minor histocompatibility (H) loci. Cells cultured for 2 to 3 days inhibit cell-mediated lympholysis specifically in that they suppress only when they carry the same H antigen by which the stimulators activate the responding cells. However, culturing of cells for more than 3 days results also in the generation of nonspecific suppressor cells which inhibit the cell-mediated lympholysis regardless whether they carry the stimulating antigens. The specific suppressor cells are T lymphocytes of the Lyt-1+Lyt-2+ type. Fresh, uncultured spleen cells, although ineffective in vitro, can prevent the in vivo priming of minor H-specific cytotoxic T lymphocyte precursors when injected i.v. into mice incompatible at minor H loci. This suppressive effect of the immunizing inoculum is abolished by irradiation (3300 rds) or by treatment with a monoclonal Thy-1-specific antibody and complement. Thus the suppressor T cell demonstrated here is of the "veto" cell type; that is, it probably suppresses minor H-specific cells when the latter recognize the stimulating antigen on the surface of the suppressor cell itself.