Multiple Defects of Immune Cell Function in Mice with Disrupted Interferon-γ Genes

Interferon-γ (IFN-γ) is a pleiotrophic cytokine with immunomodulatory effects on a variety of immune cells. Mice with a targeted disruption of the IFN-γ gene were generated. These mice developed normally and were healthy in the absence of pathogens. However, mice deficient in IFN-γ had impaired production of macrophage antimicrobial products and reduced expression of macrophage major histocompatibility complex class II antigens. IFN-γ-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-γ-deficient mice. Thus, IFN-γ is essential for the function of several cell types of the murine immune system.