title: Infection of mice lacking the common cytokine receptor gamma-chain (gamma(c)) reveals an unexpected role for CD4+ T lymphocytes in early IFN-gamma-dependent resistance to Toxoplasma gondii.
abstract: Mice lacking the common cytokine receptor gamma-chain (gamma(c)) gene exhibit defective development of NK cells and CD8+ T cells and greatly diminished production of IFN-gamma. Because resistance of SCID mice to Toxoplasma gondii requires IL-12-dependent IFN-gamma production by NK cells, we expected that gamma(c)-deficient mice would succumb rapidly to the parasite. Surprisingly, however, most gamma(c)-deficient mice survived the acute phase of T. gondii infection. As in wild-type mice, this resistance required IL-12 and IFN-gamma; nevertheless, whereas wild-type mice depleted of CD4+ T cells survived, anti-CD4+ treated gamma(c)-deficient mice displayed diminished production of IFN-gamma and all succumbed to acute infection. These data not only reveal a role for CD4+ T lymphocytes in IFN-gamma-dependent host defense but also establish SCID and gamma(c)-deficient mice as powerful complementary tools for assessing the function of NK vs CD4+ T cells in immunopathophysiologic responses.
authors.affiliation: Immunobiology Section, Laboratory of Parasitic Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: T
authors.initials: T
authors.lastname: Scharton-Kersten
authors.forename: H
authors.initials: H
authors.lastname: Nakajima
authors.forename: G
authors.initials: G
authors.lastname: Yap
authors.forename: A
authors.initials: A
authors.lastname: Sher
authors.forename: W J
authors.initials: WJ
authors.lastname: Leonard
mesh_terms: D000208:Acute Disease; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D007371:Interferon-gamma / Q000502:physiology*; D018664:Interleukin-12 / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018121:Receptors, Cytokine / Q000172:deficiency*; D014124:Toxoplasmosis, Animal / Q000276:immunology*
chemical_list: D018121:Receptors, Cytokine; D018664:Interleukin-12; D007371:Interferon-gamma