Abstract
The secretion of tumor necrosis factor (TNF)-alpha from macrophages is regulated by both priming and triggering signals. We found that macrophages from mice lacking gamma delta T cells [T cell receptor (TCR) delta-/- mice], which lack the gene encoding the delta chain, produced only small amounts of TNF-alpha in response to lipopolysaccharide (LPS) and showed a reduced level of expression of CD14. Pre-incubation of macrophages from TCR delta-/- mice with gamma delta T cells from their TCR delta +/- littermates restored their capacity to produce TNF-alpha in response to LPS. The priming activity of gamma delta T cells was in part inhibited by neutralizing anti-interferon (IFN)-gamma monoclonal antibodies. Collectively, these results suggest that gamma delta T cells play a role in priming macrophages to a steady state of activation via IFN-gamma secretion, which allows them to produce TNF-alpha when exposed to LPS.
MeSH terms
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Animals
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Antibodies, Monoclonal / immunology
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Antibodies, Monoclonal / pharmacology
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Antigens, CD / biosynthesis
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Antigens, CD / genetics
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Antigens, Differentiation, Myelomonocytic / biosynthesis
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Antigens, Differentiation, Myelomonocytic / genetics
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Chimera
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Interferon-gamma / antagonists & inhibitors
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Interferon-gamma / immunology
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Interferon-gamma / metabolism
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Lipopolysaccharide Receptors
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Lipopolysaccharides / pharmacology
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Lymphocyte Activation
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Macrophage Activation*
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Macrophages, Peritoneal / drug effects
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Macrophages, Peritoneal / metabolism
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Male
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Mice
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Mice, Inbred BALB C
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Mice, Knockout
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Receptors, Antigen, T-Cell, gamma-delta / analysis*
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Receptors, Antigen, T-Cell, gamma-delta / deficiency
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Receptors, Antigen, T-Cell, gamma-delta / genetics
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Signal Transduction*
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Specific Pathogen-Free Organisms
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T-Lymphocyte Subsets / immunology*
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Tumor Necrosis Factor-alpha / biosynthesis*
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Antibodies, Monoclonal
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Antigens, CD
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Antigens, Differentiation, Myelomonocytic
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Lipopolysaccharide Receptors
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Lipopolysaccharides
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Receptors, Antigen, T-Cell, gamma-delta
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Tumor Necrosis Factor-alpha
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Interferon-gamma