ABSTRACT
Visceral leishmaniasis is one of several parasitic diseases of humans characterized by immune suppression. A murine model of disseminated leishmaniasis utilizing inbred strains of specific genetic constitution was used to study the mechanisms of immunosuppression elicited during the course of infection. Resistant (Lshr) and susceptible (Lshs) strains of mice were challenged with amastigotes of Leishmania donovani and evaluated as to immune status at intervals between 2 and 40 weeks after challenge. The proliferative responses of splenic lymphocytes to T-cell mitogens, a B-cell mitogen, and parasite antigens were measured to evaluate the relative immune status of parasitized mice and noninfected control mice. Lymphocytes from resistant C3Heb/FeJ (C3H) mice responded normally to concanavalin A and phytohemagglutinin throughout the course of infection. Parasite antigen responses appeared 2 weeks after challenge of C3H mice and remained vigorous for periods up to 6 months. In contrast, immune suppression during infection was profound in both the curing (C57B1/10) and noncuring (B10.D2) phenotypes of Lshs congenic mice. Both Lshs strains developed severe infection as evidenced by high parasite burdens in the liver and spleen 4 to 5 weeks after challenge; splenic lymphocytes taken from these mice between 2 and 8 weeks became increasingly unresponsive to the T-cell mitogens as well as to parasite antigens. The noncuring B10.D2 mice which suffered chronic infection continued to be suppressed for as long as 40 weeks. C57B1/10 (curing) mice, in contrast, cleared infection between 12 and 16 weeks. After spontaneous recovery or elimination of parasites by antimonial drug therapy, the response of spleen cells to T-cell mitogens or parasite antigens were restored to normal. The spleen cells from the Lshs strains of mice obtained during the height of infection suppressed the proliferative responses of spleen cells from their uninfected counterparts upon cocultivation in vitro. Removal of adherent cells from the suppressive spleen cell populations restored normal mitogen responses. On the basis of adherence characteristics, phagocytosis, and morphology, the suppressor was identified as a macrophage population which appears to be responsible for a nonspecific immunosuppression of Lshs mice with significant parasite burdens of L. donovani.
