Tumor necrosis factor is involved in the T cell-independent pathway of macrophage activation in scid mice
Bancroft, G.J.; Sheehan, K.C.; Schreiber, R.D.; Unanue, E.R.
Journal of Immunology 143(1): 127-130
1989
ISSN/ISBN: 0022-1767 PMID: 2499625 Document Number: 330896
We analyzed the T cell-independent production of IFN-gamma in the severe combined immunodeficiency (scid) mutant mouse. Spleen cells from scid mice secreted high levels of IFN-gamma in response to heat-killed Listeria monocytogenes (HKLM), but not to the T cell stimulus ConA. This response was ablated by prior removal of adherent macrophages. IFN-gamma 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-gamma 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.