Tumor necrosis factor is involved in the T cell-independent pathway of macrophage activation in scid mice

We analyzed the T cell-independent production of IFN-γ in the severe combined immunodeficiency (scid) mutant mouse. Spleen cells from scid mice secreted high levels of IFN-γ in response to heat-killed Listeria monocytogenes (HKLM), but not to the T cell stimulus Con A. This response was ablated by prior removal of adherent macrophages. IFN-γ secretion in vitro was preceded by the rapid production of TNF and was inhibited by addition of neutralizing mAb to TNF. Moreover, injection of scid mice with anti-TNF mAb increased the severity of infection with live Listeria and inhibited macrophage activation for class II-MHC expression. Finally, IFN-γ secretion and class II-MHC expression were also inhibited by an antibody to asialoGM₁, a reagent known to impair host NK cell function. These results suggest that TNF is a critical cytokine in the T cell-independent pathway of macrophage activation in scid mice.