Immunosuppression in Experimental African Trypanosomiasis

Abstract

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.

Involvement of suppressor cells induced with membrane fractions of trypanosomes in immunosuppression of trypanosomiasis

“…Our results suggest some non-constant feature on the VSG molecule could be involved in the signal for suppression. This is of interest in view of the reports of Assoku, Hazlett & Tizard (1979) and Sacks et al (1982) that a high molecular weight fraction containing lipid mediated both the mitogenic and immunosuppressive effect of T. congolense and T. b. brucei infections. It could be that the differences in immunosuppression we observe could be due to regions of the VSG molecule associated with the membrane, where isotypic or other amino acid sequence variations are observed.…”

Early course of infection in susceptible and resistant strains of mice, using [3H]uridine-labeled Trypanosoma brucei subsp. brucei

“…African trypanosomes are often observed within lymphoid tissue (6,27) and produce a suppression (1,11,16,17,19,23) or an activation (or both) of the lymphocytes of the spleen, lymph nodes, and peripheral blood. The spleens of both Swiss-Webster and deer mice were found to accumulate label associated with viable trypanosomes, indicating that spleen cells at an early stage of infection are exposed to soluble (20) and membranous (4) trypanosome components with immunosuppressive characteristics.…”