Regulation of cytotoxic reactivity to minor histocompatibility antigens by administration of Corynebacterium parvum.

B10.BR(H-2k) mice were primed with H-2-identical allogeneic CBA/J(H-2k) spleen cells and restimulated in vitro 14 days later to generate specific secondary cytotoxic lymphocytes. A single intravenous injection of primed mice with 700 micrograms of Corynebacterium parvum 7 days after alloimmunization markedly inhibited the subsequent secondary in vitro generation of cytotoxic cells. In addition, regulatory spleen cells were detected in alloimmunized C-parvum-injected mice that prevented the restimulation of primed control spleen cells. Suppressive activity could not be abrogated by treating regulatory cells with anti-theta antibody and complement or by removing phagocytic cells, but it was overcome by treatment with mitomycin C. Unfractionated regulatory cells suppressed responses in an antigen nonspecific fashion. However, cells remaining after carbonyl and iron treatment (nonphagocytic) could no longer suppress responses to third party alloantigens while maintaining significant suppression of anti-CBA responses. These data suggest the generation of two distinct suppressor cell types that can control the cytotoxic response to minor histocompatibility antigens: an antigen-nonspecific phagocytic cell and an antigen specific nonphagocytic, non-theta-bearing cell.