Science, Vol 259, Issue 5102, 1739-1742
Copyright © 1993 by American Association for the Advancement of Science
Multiple defects of immune cell function in mice with disrupted interferon-gamma genes
DK Dalton,
S Pitts-Meek,
S Keshav,
IS Figari,
A Bradley,
and
TA Stewart
Genentech Inc., South San Francisco, CA 94080.
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.
