title: Requirement for T cells and effect of lymphokines in successful chemotherapy for an intracellular infection. Experimental visceral leishmaniasis.
abstract: Although directly microbicidal, pentavalent antimony has failed as treatment for visceral leishmaniasis in patients who also have AIDS or are receiving immunosuppressive therapy. To define the role of T cells in the successful host response to chemotherapy, we examined the efficacy of pentavalent antimony (sodium stibogluconate, Pentostam) in normal and T cell-deficient BALB/c mice infected with Leishmania donovani. In euthymic (nu/+) mice, single injections of 250 and 500 mg/kg of Pentostam induced the killing of 67% and 89% of intracellular liver amastigotes, respectively. In contrast, in athymic nude (nu/nu) mice, up to three injections of 500 mg/kg achieved no L. donovani killing and did not retard visceral parasite replication. Once nude mice were reconstituted with nu/+ spleen cells, however, Pentostam exerted strong leishmanicidal activity, an effect that appeared to be transferred by either L3T4+ or Lyt-2+ cells. Responsiveness to chemotherapy could also be induced by providing nude mice with either interferon-gamma or interleukin 2 alone. The absence of this T cell- and probably lymphokine-dependent mechanism is a likely explanation for treatment failures in immunocompromised patients infected with L. donovani and perhaps other systemic intracellular pathogens as well.
authors.affiliation: Division of Infectious Diseases, Cornell University Medical College, New York 10021.
authors.forename: H W
authors.initials: HW
authors.lastname: Murray
authors.forename: M J
authors.initials: MJ
authors.lastname: Oca
authors.forename: A M
authors.initials: AM
authors.lastname: Granger
authors.forename: R D
authors.initials: RD
authors.lastname: Schreiber
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte; D000950:Antigens, Ly; D000967:Antimony Sodium Gluconate / Q000627:therapeutic use*; D001826:Body Fluids / Q000187:drug effects*; D005260:Female; D005942:Gluconates / Q000627:therapeutic use*; D007113:Immunity, Innate / Q000187:drug effects; D007371:Interferon-gamma / Q000494:pharmacology* / Q000627:therapeutic use; D007376:Interleukin-2 / Q000494:pharmacology* / Q000627:therapeutic use; D007424:Intracellular Fluid / Q000187:drug effects*; D007898:Leishmaniasis, Visceral / Q000188:drug therapy* / Q000276:immunology / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010641:Phenotype; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000145:classification / Q000187:drug effects* / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000945:Antigens, Differentiation, T-Lymphocyte; D000950:Antigens, Ly; D005942:Gluconates; D007376:Interleukin-2; D011994:Recombinant Proteins; D007371:Interferon-gamma; D000967:Antimony Sodium Gluconate