title: CD4+ effector cells default to the Th2 pathway in interferon gamma-deficient mice infected with Leishmania major.
abstract: Mice with homologous disruption of the interferon gamma (IFN-gamma) gene on the C57BL/6 background were infected with Leishmania major and the immune response assessed. In contrast to wild-type or heterozygous knockout mice, deficient animals were unable to restrict growth of the parasite and suffered lethal infection over 6-8 wk. Although wild-type and heterozygous littermates developed CD4+ cells that contained transcripts for IFN-gamma and lymphotoxin, typical of T helper type 1 (Th1) cells, the knockout mice developed CD4+ cells that contained transcripts for interleukin 4 (IL-4), IL-5, and IL-13, typical of Th2 cells. ELISPOT assays confirmed the reciprocal patterns of IFN-gamma or IL-4 production by T cells in similar frequencies in the respective groups of mice, and antibody analysis confirmed the presence of Th2-mediated isotype switching in the knockout mice. These data suggest that CD4+ T cells that normally respond to antigens by differentiation to Th1 cells default to the Th2 pathway in the absence of endogenous IFN-gamma.
authors.affiliation: Department of Medicine, University of California San Francisco 94143.
authors.forename: Z E
authors.initials: ZE
authors.lastname: Wang
authors.forename: S L
authors.initials: SL
authors.lastname: Reiner
authors.forename: S
authors.initials: S
authors.lastname: Zheng
authors.forename: D K
authors.initials: DK
authors.lastname: Dalton
authors.forename: R M
authors.initials: RM
authors.lastname: Locksley
mesh_terms: D000818:Animals; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016054:DNA, Protozoan; D006579:Heterozygote; D007371:Interferon-gamma / Q000172:deficiency* / Q000235:genetics; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
chemical_list: D016054:DNA, Protozoan; D007371:Interferon-gamma