Response to treatment for an intracellular infection in a T cell-deficient host: Toxoplasmosis in nude mice
To examine the experimental basis of treatment failures in T cell-deficient patients with intracellular infections, euthymic and athymic (nude) BALB/c mice were infected with Toxoplasma gondii and treated with sulfadiazine. All euthymic and nude mice survived during 2 weeks of sulfadiazine therapy. Once treatment was discontinued, 100% of euthymic mice survived while all nude mice died. Post-sulfadiazine treatment survival was enhanced in nude mice by reconstitution with either L3T4+ or Lyt-2+ cells and was reduced in euthymic mice by monoclonal antibody treatment directed at depleting either L3T4+ or Lyt-2+ cells or interleukin-2 (IL-2) or interferon-gamma (IFN-gamma). These results suggest that although T cells and their products are not required for an initial response (survival) to treatment in acute experimental toxoplasmosis, survival off drug is strictly T cell-dependent. Optimal posttreatment survival appears to involve both L3T4+ helper and Lyt-2+ cytotoxic cells, probably acting in concert, as well as the endogenous secretion of at least two T cell-derived lymphokines, IL-2 and IFN-gamma.