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.
Murray
H W
HW
Division of Infectious Diseases, Cornell University Medical College, New York, New York 10021.
Teitelbaum
R
R
Hariprashad
J
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002478:Cells, Cultured; D005260:Female; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D013411:Sulfadiazine / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000276:immunology*; D014124:Toxoplasmosis, Animal / Q000188:drug therapy* / Q000276:immunology; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D013411:Sulfadiazine