Immunosuppression in experimental African trypanosomiasis. Polyclonal B-cell activation and mitogenicity of trypanosome-derived saturated fatty acids.

Changes in antibody responses in adult mice infected with Trypanosoma congolense and subsequently challenged with unrelated antigens (sheep red blood cells and pneumococcal polysaccharide) were studied. Immune responses were significantly depressed within 1 week of infection, and complete suppression of both IgM and IgG responses to both types of antigen was established 15 days after immunization. Coincidentally with the development of high parasitaemias, background IgM plaque-forming cell responses to sheep red cell antigen significantly increased in non-immunized T. congolense-infected animals. Autolysates of T. congolense and chloroform-soluble extracts of the autolyzed trypanosome were found to be mitogenic in vitro for the spleen cells of normal mice. Fractionation of these extracts by thin-layer chromatography indicated that the mitogenic activity migrated with the free fatty acids. Substitution of the relevant saturated and unsaturated free fatty acids in the autolyzed trypanosome extracts with commercial pure fatty acids in the mouse spleen cultures indicated that the mitogenicity was due to palmitic and stearic acids. It is suggested that the general immunosuppressing effect of trypanosomes may be attributed, at least in part, to the polyclonal activation, and subsequent depletion and/or clonal exhaustion of B-cells as a result of blastogenic stimulus from the parasites. This may operate, at least in part, through the generation of B-cell mitogenic saturated fatty acids.

The immunosuppressive and mitogenic effects of Trypanosoma musculi.

In CD-1 mice infected with Trypanosoma musculi, the production of IgM and IgG antibodies in response to sheep erythrocytes (SRBC) was significantly suppressed when mice were immunized with SRBC once high parasitaemias had developed. In infected mice which were not immunized with SRBC, background plaque-forming responses of spleen cells to SRBC were significantly higher than in uninfected, unimmunized mice. Factors derived from T. musculi were found to be mitogenic in vitro for spleen cells taken from CD-1 mice. The mitogenic response to these factors by spleen cells from athymic mice was highly significant, whereas the response of spleen cells taken from CD-1 mice which had been pre-treated with cyclophosphamide was much less, suggesting that the B cell was the major target of the trypanosome-derived mitogen. In this paper we discuss the possible relationship of T. musculi-induced mitogenesis to the immunosuppression and non-specific antibody formation associated with T. musculi infections.