title: Antimicrobial response of a T cell-deficient host to cytokine therapy: effect of interferon-gamma in experimental visceral leishmaniasis in nude mice.
abstract: To determine if interferon (IFN)-gamma can enhance intracellular antimicrobial defense in a T cell-deficient host, nude BALB/c mice were infected with Leishmania donovani and treated with IFN-gamma. IFN-gamma induced killing of L. donovani in livers of euthymic mice but had no effect in nude mice despite activating peritoneal macrophages in vivo. Transfer of CD4+ or CD8+ T cells permitted nude mice to respond to IFN-gamma; treatment with T cell-regulated antileishmanial cytokines (interleukin-2, granulocyte-macrophage colony-stimulating factor, or tumor necrosis factor-alpha) could not substitute for T cells. NK cells played no apparent role. In reconstituted nude mice, the antileishmanial effect of IFN-gamma correlated with markedly enhanced mononuclear cell recruitment to infected liver foci. Thus, although IFN-gamma activates macrophages in the absence of host T cells, a T cell mechanism is required for antileishmanial activity in tissue. Provided one T cell subset is adequately preserved, IFN-gamma may prove useful in intracellular infections in the T cell-deficient host.
authors.affiliation: Division of Infectious Diseases, Cornell University Medical College, New York, New York, USA.
authors.forename: H W
authors.initials: HW
authors.lastname: Murray
authors.forename: J
authors.initials: J
authors.lastname: Hariprashad
authors.forename: B
authors.initials: B
authors.lastname: Aguero
authors.forename: T
authors.initials: T
authors.lastname: Arakawa
authors.forename: H
authors.initials: H
authors.lastname: Yeganegi
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D016207:Cytokines / Q000627:therapeutic use; D005260:Female; D007371:Interferon-gamma / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000276:immunology; D007893:Leishmania donovani / Q000187:drug effects*; D007898:Leishmaniasis, Visceral / Q000276:immunology / Q000628:therapy*; D008099:Liver / Q000276:immunology / Q000469:parasitology; D008262:Macrophage Activation; D017737:Macrophages, Peritoneal / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011994:Recombinant Proteins
chemical_list: D016207:Cytokines; D011994:Recombinant Proteins; D007371:Interferon-gamma