Macrophages as primary target cells and mediators of immune dysfunction in African trypanosomiasis

African trypanosomiasis is accompanied by profound general immunosuppression. The experiments described here were designed to characterize the contribution of macrophages to the immune pathology of this disease. We used peptone-stimulated, uninfected mice and injected them intraperitoneally with lethally irradiated and 35S-labeled Trypanosoma brucei and parasite-specific antisera. Peritoneal macrophages were thus induced to take up in vivo a defined number of trypanosomes. After the phagocytosis of parasites, macrophages were transferred into uninfected syngeneic mice, where they mimicked some of the important immunological changes normally associated with active trypanosome infection: (i) splenic background plaque-forming cells increased nonspecifically and (ii) the specific immune response to sheep erythrocytes was either enhanced or suppressed, depending on the timing of the antigen challenge: priming simultaneously with the transfer of trypanosome-containing macrophages enhanced immune responsiveness; in contrast, if parasite-containing macrophages were transferred and recipient mice were primed 4 days later, the immune response was suppressed. A contribution of suppressor T cells was ruled out by the treatment of peritoneal exudate cells with anti-Thy 1.2 and complement before transfer into recipient mice. The results indicate that macrophages are key cells in the mediation of parasite-induced immune dysfunction.