CD4+ effector cells default to the Th2 pathway in interferon gamma-deficient mice infected with Leishmania major.

作者：Z E Wang, Steven L. Reiner, Shichun Zheng, Dyana K. Dalton, Richard M. Locksley · 发表于：The Journal of Experimental Medicine · 年份：1994 · DOI：10.1084/jem.179.4.1367 · 被引用次数：396 · 研究领域：Research on Leishmaniasis Studies、Autoimmune and Inflammatory Disorders Research、Immunotoxicology and immune responses

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.