The addition of heavily irradiated or mitomycin-treated spleen cells to cultures containing syngeneic spleen cells and foreign erythrocytes may stimulate to some extent the hemolytic plaque-forming cell responses of these cultures, but the addition of semi-allogeneic irradiated or mitomycin-treated spleen cells may cause much greater stimulation. This semi-allogeneic stimulation is completely reciprocal; the plaque-forming cell responses of F1 hybrid spleen cell cultures often are stimulated as much after the addition of non-proliferating parental cells as are the responses of parental spleen cell cultures after the addition of non-proliferating F1 hybrid cells. The possibility that an in vitro manifestation of hybrid resistance might be involved was ruled out. It was found that irradiated or mitomycin-treated cells, although unable to proliferate, were still able to initiate a recognition reaction against histoincompatible cells, releasing in the process a soluble factor which stimulated proliferation of cells of the antibody-forming series. The significance of this finding for “one-way” mixed lymphocyte reactions is discussed.

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