THE ROLE OF GAMMA-DELTA T-CELLS IN PRIMING MACROPHAGES TO PRODUCE TUMOR-NECROSIS-FACTOR-ALPHA

The secretion of tumor necrosis factor (TNF)-alpha from macrophages is regulated by both priming and triggering signals. We found that macro phages from mice lacking gamma delta T cells [T cell receptor (TCR) de lta(-/-) mice], which lack the gene encoding the delta chain, produced only small amounts of TNF-alpha in response to lipopolysaccharide (LP S) and showed a reduced level of expression of CD14. Pre-incubation of macrophages from TCR delta(-/-) mice with gamma delta T cells from th eir TCR delta(+/-) littermates restored their capacity to produce TNF- cr in response to LPS. The priming activity of gamma delta T cells was in part inhibited by neutralizing anti-interferon (IFN)-gamma monoclo nal antibodies. Collectively, these results suggest that gamma delta T cells play a role in priming macrophages to a steady state of activat ion via IFN-gamma secretion, which allows them to produce TNF-alpha wh en exposed to LPS.