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

• Published in: The Journal of experimental medicine 1994-04, Vol.179 (4), p.1367-1371
• Main Authors: ZHI-EN WANG, REINER, S. L, SHICHUN ZHENG, DALTON, D. K, LOCKSLEY, R. M
• Format: Article
• Language: English
• Subjects: Animals; Base Sequence; Biological and medical sciences; CD4-Positive T-Lymphocytes - immunology; DNA, Protozoan; Experimental protozoal diseases and models; Heterozygote; Infectious diseases; Interferon-gamma - deficiency; Interferon-gamma - genetics; Leishmania major - immunology; Leishmaniasis, Cutaneous - immunology; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Molecular Sequence Data; Parasitic diseases; Protozoal diseases; T-Lymphocytes, Helper-Inducer - immunology
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.179.4.1367

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.