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-defi cient patients with intracellular infections, euthymic and athymic (nu de) BALB/c mice were infected with Toxoplasma gondii and treated with sulfadiazine. All euthymic and nude mice survived during 2 weeks of su lfadiazine therapy. Once treatment was discontinued, 100% of euthymic mice survived while all nude mice died. Post-sulfadiazine treatment su rvival was enhanced in nude mice by reconstitution with either L3T4+ o r Lyt-2+ cells and was reduced in euthymic mice by monoclonal antibody treatment directed at depleting either L3T4+ or Lyt-2+ cells or inter leukin-2 (IL-2) or interferon-gamma (IFN-gamma). These results suggest that although T cells and their products are not required for an init ial response (survival) to treatment in acute experimental toxoplasmos is, survival off drug is strictly T cell-dependent. Optimal posttreatm ent survival appears to involve both L3T4+ helper and Lyt-2+ cytotoxic cells, probably acting in concert, as well as the endogenous secretio n of at least two T cell-derived lymphokines, IL-2 and IFN-gamma.