Nonimmune lymphoid cells were capable of causing cytotoxicity of H-2 incompatible mouse tumor cells in vitro in the presence of PHA, whereas syngeneic cells were not. Semisyngeneic and X-irradiated (1500–3000 R) F1 hybrid lymphoid cells were cytotoxic for target cells derived from one of the parental strains. In addition, parental nonimmune and X-irradiated lymphoid cells damaged hybrid target cells. It was concluded that one component of cytotoxicity was not related to an induction of a primary immune response in vitro, since F1 hybrid cells are not capable of reacting immunologically against parental type target cells. It seemed probable that cytotoxicity was caused by target cell confrontation with antigenically and/or structurally incompatible lymphoid cells. This conclusion was strengthened by the demonstration that isoantibodies produced in the target strain and directed against the allogeneic lymphoid cells specifically suppressed cytotoxicity. Isoantibodies reacting against some but not all of the antigenic determinants of the lymphoid cells differentiating them from the target cells did not suppress cytotoxicity. The specific suppression of cytotoxicity by specific isoantibodies against the lymphoid cells support the allogeneic inhibition concept.

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