An adherent, phagocytic, non-T cell present in the spleen of BCG infected animals was found capable of inhibiting both primary and secondary cytotoxic responses to alloantigen in vitro. BCG-spleen cells were compared to suppressor T cell populations induced either by culturing spleen cells in 10% fetal calf serum for periods up to 5 days or by stimulation of splenocytes for 48 hr with 5 µg/ml Con A. These comparative studies revealed that i) all suppressor cell populations were less effective at inhibiting secondary cytotoxic responses than they were at suppressing primary responses. ii) BCG-induced suppressor macrophages were as effective on a spleen cell basis as Con A-induced suppressor T cells. Both of these populations were superior to suppressor T cells induced by culture in the absence of added mitogen, which had little or no effect on secondary responses.
More importantly, both BCG and Con A-induced suppressor cells were capable of inhibiting the development of cytotoxic cells in cultures containing mitomycin C-treated “memory” cells. Thus, these suppressor cells can prevent nonproliferative events associated with cytotoxic T cell differentiation. It is therefore conceivable that the widely reported anti-proliferative action of suppressor cells is a secondary effect, resulting from suppression of a differentiative event that precedes cell proliferation.
This work was supported by Grant CA22979 from the National Cancer Institute.