Multiple defects of immune cell function in mice with disrupted interferon-gamma genes.
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.
Dalton
D K
DK
Genentech Inc., South San Francisco, CA 94080.
Pitts-Meek
S
S
Keshav
S
S
Figari
I S
IS
Bradley
A
A
Stewart
T A
TA
D000818:Animals; D002455:Cell Division; D003602:Cytotoxicity, Immunologic; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007109:Immunity; D007371:Interferon-gamma / Q000235:genetics* / Q000502:physiology; D007519:Isoantigens / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D009163:Mycobacterium bovis; D009569:Nitric Oxide / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection; D014376:Tuberculosis / Q000276:immunology
D000949:Histocompatibility Antigens Class II; D007519:Isoantigens; D009569:Nitric Oxide; D007371:Interferon-gamma