Demonstration of T-cell dysfunction during acute toxoplasma infection.
Mice were infected with the virulent RH and the relatively avirulent C56 strains of Toxoplasma gondii (TG). The concanavalin A (Con A)-stimulated lymphoproliferative response of these animals and interleukin-2 (IL-2) production by their lymphocytes were assessed 3 and 6 days postinfection. The proliferative response of splenocytes (SC) and T-enriched cells from all infected groups was significantly (P less than 0.05-0.005) depressed. Partial removal of macrophages (m phi) or addition of indomethacin had no effect on the depressed proliferative response of SC from mice infected with the RH strain of TG for 6 days (RH6), and only partially improved that from the other infected groups. IL-2 production of T-enriched cells, obtained by scrupulously removing m phi using sequential adherence of SC to plastic and nylon wool, was markedly decreased in all infected mice. These data indicate that both m phi and T cells are involved in the immunodepression in toxoplasmosis. Except for the RH6 group, the depressed lymphoproliferative responses of all infected groups were entirely reconstituted by exogenous IL-2, but their peak response never reached that of the control group. Therefore, the decreased lymphoproliferation could not be explained solely by a defect in IL-2 production. The proliferative response of the RH6 lymphocytes, in the presence of Con A, was significantly lower than without Con A at each IL-2 concentration added. This suggests the presence of an active suppressor factor inducible by Con A. The RH strain of TG caused a greater degree of immunodepression than the C56 strain, suggesting an association between the virulence of different strains of TG with their ability to immunosuppress.
D000208:Acute Disease; D000818:Animals; D003208:Concanavalin A / Q000494:pharmacology; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014124:Toxoplasmosis, Animal / Q000276:immunology*
D007376:Interleukin-2; D003208:Concanavalin A; D007213:Indomethacin