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Interferon-gamma (IFN-gamma) is a pleiotrophic cytokine with immunomodulatory effects on a variety of immune cells. Mice with a targeted disruption of the IFN-gamma gene were generated. These mice developed normally and were healthy in the absence of pathogens. However, mice deficient in IFN-gamma had impaired production of macrophage antimicrobial products and reduced expression of macrophage major histocompatibility complex class II antigens. IFN-gamma-deficient mice were killed by a sublethal dose of the intracellular pathogen Mycobacterium bovis. Splenocytes exhibited uncontrolled proliferation in response to mitogen and alloantigen. After a mixed lymphocyte reaction, T cell cytolytic activity was enhanced against allogeneic target cells. Resting splenic natural killer cell activity was reduced in IFN-gamma-deficient mice. Thus, IFN-gamma is essential for the function of several cell types of the murine immune system.

Type

Journal article

Journal

Science

Publication Date

19/03/1993

Volume

259

Pages

1739 - 1742

Keywords

Animals, Cell Division, Cytotoxicity, Immunologic, Histocompatibility Antigens Class II, Immunity, Interferon-gamma, Isoantigens, Killer Cells, Natural, Lymphocyte Culture Test, Mixed, Macrophages, Mice, Mice, Inbred C57BL, Mice, Transgenic, Mutation, Mycobacterium bovis, Nitric Oxide, Spleen, T-Lymphocytes, Transfection, Tuberculosis