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-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.
Bancroft
G J
GJ
Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110.
Sheehan
K C
KC
Schreiber
R D
RD
Unanue
E R
ER
D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology; D000955:Antigens, T-Independent / Q000276:immunology*; D007153:Immunologic Deficiency Syndromes / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology; D008088:Listeriosis / Q000276:immunology; D008262:Macrophage Activation; D051379:Mice; D008817:Mice, Mutant Strains; D013154:Spleen / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000502:physiology*
D000911:Antibodies, Monoclonal; D000955:Antigens, T-Independent; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma