A T cell-independent mechanism of macrophage activation by interferon-γ

A primary interest in immunity to intracellular pathogenic microorganisms and tumors is to understand the mechanisms by which macrophages are activated for various functions. Two parameters of macrophage activation are the expression of the class II histocompatibility proteins or Ia molecules (1), and cytotoxic activity. The ability of T cells to induce these responses has been extensively documented and occurs via their secretion of interferon-γ (IFN-γ) after interaction with antigen (2-6). However, in a recent study using mice with the severe combined immunodeficiency (scid)³ mutation (7) which have no detectable T or B cell functions (7-9), we were surprised to find the induction of Ia expression on macrophages and the partial inhibition of bacterial growth after infection with Listeria monocytogenes (10). We have now utilized neutralizing monoclonal antibodies specific for murine IFN-γ to investigate the mechanism of macrophage activation in scid mice. We show here that IFN-γ can be produced by scid mice in the absence of lymphocyte-mediated immunity, and this IFN-γ is important for macrophage activation during infection with Listeria. These results indicate the presence of an important T lymphocyte-independent mechanism of macrophage activation and IFN-γ production in response to infection.