Trypanosoma cruzi: regulation of mitogenic responses during infection in genetically resistant and susceptible inbred mouse strains.
The outcome of Trypanosoma cruzi infection in inbred strains of mice is under genetic control. The lymphocyte responses to T-cell mitogens and their regulation were investigated in strains of mice resistant or susceptible to T. cruzi. Six to eight days after the inoculation of T. cruzi, resistant and susceptible mice had depressed responses to T-cell mitogens. In resistant B6 mice, suppression was maximal 18 days after infection and it persisted for at least 320 days. The duration of immunosuppression correlated with the persistence of a subpatent parasitemia. In cell mixing experiments, it was determined that the concanavalin A (Con A) responses in the resistant B6 and B6C3F1 mouse strains were suppressed by highly active T-suppressor cells. In the susceptible C3H mice, intense suppression of the Con A responses was detected 14 days after inoculation of T. cruzi. Nevertheless, only weak suppressor cell activity was detected in the infected C3H mice, and suppression was not abrogated by passage through a nylon wool column nor by treatment with antitheta antibodies and complement. Thus, it was suggested that, during the course of infection with T. cruzi, splenic T cells from C3H mice acquired a block in the metabolic pathway for cellular activation by Con A. The influences of T. cruzi epimastigotes on the Con A responses of spleen cells from uninfected mice were then studied. The Con A responses of spleen cells from C3H mice were depressed in the presence of epimastigotes, whereas they were either unaffected or enhanced in spleen cells from B6 mice. Hence, the immunoregulatory events provoked by T. cruzi infection differed in genetically resistant and susceptible mice, and lymphocytes from C3H mice were predisposed to a parasite-induced block in the responses to Con A. Thus, the gene(s) determining the outcome of infection with T. cruzi may be phenotypically expressed through an influence on immunoregulatory events.
Lalonde
R G
RG
Ali-Khan
Z
Z
Tanowitz
H B
HB
D000818:Animals; D014355:Chagas Disease / Q000235:genetics / Q000276:immunology*; D003208:Concanavalin A / Q000494:pharmacology; D005260:Female; D005796:Genes; D007108:Immune Tolerance; D007113:Immunity, Innate; D008213:Lymphocyte Activation; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D003208:Concanavalin A