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 < 0.05-0.005) depressed. Partial removal of macrophages (mφ) 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 mφ using sequential adherence of SC to plastic and nylon wool, was markedly decreased in all infected mice. These data indicate that both mφ 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 that 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.