Generation of disparate immunoregulatory factors in two inbred strains of mice with disseminated histoplasmosis.

Abstract

Suppressor cells are generated within the spleens of C3H/HeJ and C57BL/6 mice during the first 4 wk of systemic infection with Histoplasma capsulatum ( He). To determine if splenic suppressor cells produce soluble immunoregulatory factors during the course of He infection, supernatants from spleen cell cultures of control and infected C3H/HeJ and C57BL/6 mice were harvested at 4 days and tested for their ability to modulate the primary in vitro antibody response to sheep red blood cells by normal syngeneic spleen cells. At 1 wk of infection, supernatants from spleen cell cultures of infected C3H/HeJ mice markedly suppressed the response of normal spleen cells. In contrast, supernatants from spleen cell cultures of infected C57BL/6 mice substantially enhanced the response of normal spleen cells. After 1 wk, supernatants from infected mice did not demonstrate significant amounts of immunoregulatory activity.The suppressor factor from C3H/HeJ mice with Hc infection (SF-H) was inactivated by trypsin, pH 2.2 and 56°C, but not by DNase and RNase. Conversely, the helper factor from C57BL/6 mice with He infection (HF-H) was inactivated by trypsin and 100°C but not by pH 2.2, 56°C, DNase, or RNase. Approximate m.w. of SF-H and HF-H were 25,000 and 29,000, respectively. HF-H and SF-H modulated the in vitro antibody response only when added during the first 24 hr of culture. Thus, two disparate immunoregulatory factors are produced by spleen cells that are immunosuppressive in vitro. To our knowledge, this is the first report of the production of a nonspecific helper factor by cells that mediate suppression. Both SF-H and HF-H may be important in the perturbations of immunoregulation associated with disseminated histoplasmosis.