Regulation of macrophage suppression and cytotoxicity by interferon role of Ia-bearing macrophages.

Abstract

Resident peritoneal M phi of C3H/HeN mice co-cultured with splenic lymphocytes suppressed proliferation to mitogens. This M phi-mediated suppression was significantly reduced by in vitro treatment of M phi with fibroblast interferon (IFN-beta). Conversely, M phi-mediated natural tumor cytolysis was augmented by M phi treatment with IFN-beta. Depletion of Ia-bearing (Ia+) M phi by means of anti-Ia serum and C treatment did not affect M phi-mediated suppression or M phi-mediated natural cytotoxicity. This suggested that Ia-negative (Ia-) M phi were responsible for the effector phase of these two M phi functions. The IFN-beta-induced increase in M phi cytolysis was not affected by depletion of Ia+ cells; however, modulation of suppressive activity by IFN-beta was found to be highly dependent on the presence of Ia+ M phi. This observation indicated that different M phi subpopulations were involved in the regulation of suppressive and tumoricidal activity. The results indicating different regulatory M phi were supported by experiments with C3H/HeJ mice. C3H/HeJ M phi do not develop high cytolytic activity in response to a variety of stimuli; however, M phi from C3H/HeJ mice were able to exert suppressive activity, which was reduced by treatment with IFN-beta.