The role of γδ T cells in priming macrophages to produce tumor necrosis factor‐α

The secretion of tumor necrosis factor (TNF)‐α from macrophages is regulated by both priming and triggering signals. We found that macrophages from mice lacking γδ T cells [T cell receptor (TCR) δ^−/‐ mice], which lack the gene encoding the δ chain, produced only small amounts of TNF‐α in response to lipopolysaccharide (LPS) and showed a reduced level of expression of CD14. Pre‐incubation of macrophages from TCR δ‐/‐ mice with γδ T cells from their TCR δ^+/‐ littermates restored their capacity to produce TNF‐α in response to LPS. The priming activity of γδ T cells was in part inhibited by neutralizing anti‐interferon (IFN)‐γ monoclonal antibodies. Collectively, these results suggest that γδ T cells play a role in priming macrophages to a steady state of activation via IFN‐γ secretion, which allows them to produce TNF‐α when exposed to LPS.