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In tissue culture, immune lymph node cells containing foreign histocompatibility antigens of the H-2 type exert marked cytotoxic effects on tumor cells incompatible with the H-2 antigen. An equally pronounced effect is obtained when normal allogeneic and semi-isologous lymphoid cells of F(1) hybrids are caused to aggregate around the target tumor cells by treating the cultures with either heat-inactivated rabbit antiserum to mouse cells or phytohemagglutinin. Isologous lymph node cells have no effect. Thus, aggregation of lymphoid cells and target cells is a necessary but insufficient requirement for cytotoxicity in vitro; in addition, close contact must be established between histoincompatible cells.

The ability of specifically immunized lymphoid cells to kill H-2 incompatible target tumor cells in tissue culture was shown to depend on the source of the lymphoid tissue (spleen versus lymph nodes). Marked cytotoxic effects were obtained with regional lymph node cells 7 to 10 days after primary immunization, whereas spleen cells from the same animals had little or no effect. Hyperimmunization did not decrease the cytotoxic efficiency of lymph node cells. Experiments were performed to test the possibility that the weak effect of spleen cells is a result of humoral antibody production, antagonizing the cell-bound immunity. Humoral antibodies were cytotoxic in vitro in the presence of complement only. Their effect was manifested after 2 hours, whereas immune lymph node cells did not require complement and cytotoxicity was not expressed until 24 to 48 hours' incubation. Tumor cell cultures treated with specific humoral antibodies in the absence of complement became resistant to the cytotoxic effect of subsequently added immune lymph node cells, while no such protection was seen when normal serum was added. Thus, humoral antibodies led to an "efferent" inhibition of cell-bound immunity in vitro, in analogy with previous results in vivo.