CD4+ effector cells default to the Th2 pathway in interferon gamma-deficient mice infected with Leishmania major.
Open Access
- 1 April 1994
- journal article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 179 (4), 1367-1371
- https://doi.org/10.1084/jem.179.4.1367
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.Keywords
This publication has 24 references indexed in Scilit:
- Mice that lack the interferon-gamma receptor have profoundly altered responses to infection with Bacillus Calmette-Guérin and subsequent challenge with lipopolysaccharide.The Journal of Experimental Medicine, 1993
- A common precursor for CD4+ T cells producing IL-2 or IL-4.The Journal of Immunology, 1992
- Production of interferon gamma, interleukin 2, interleukin 4, and interleukin 10 by CD4+ lymphocytes in vivo during healing and progressive murine leishmaniasis.Proceedings of the National Academy of Sciences of the United States of America, 1991
- Generation of interleukin 4 (IL-4)-producing cells in vivo and in vitro: IL-2 and IL-4 are required for in vitro generation of IL-4-producing cells.The Journal of Experimental Medicine, 1990
- Lymphokine Control of In Vivo Immunoglobulin Isotype SelectionAnnual Review of Immunology, 1990
- Cure of murine leishmaniasis with anti-interleukin 4 monoclonal antibody. Evidence for a T cell-dependent, interferon gamma-independent mechanism.The Journal of Experimental Medicine, 1990
- Administration of monoclonal anti-IFN-gamma antibodies in vivo abrogates natural resistance of C3H/HeN mice to infection with Leishmania major.The Journal of Immunology, 1989
- TH1 and TH2 Cells: Different Patterns of Lymphokine Secretion Lead to Different Functional PropertiesAnnual Review of Immunology, 1989
- Enumeration of single IFN-gamma-producing cells in mice during viral and bacterial infection.The Journal of Immunology, 1989
- Cloning and expression of murine lymphotoxin cDNA.The Journal of Immunology, 1987