Abstract
In a screen to identify genes induced by NF-kappaB/Rel transcription factors, we cloned a novel gene, b7h, that is a close homolog of B7 costimulatory ligands expressed on antigen-presenting cells. B7h can costimulate proliferation of purified T cells through a receptor on T cells distinct from CD28 or CTLA-4. Surprisingly, although B7h is expressed in unstimulated B cells, its expression is induced in both 3T3 cells and embryonic fibroblasts treated with TNFalpha, and it is upregulated in nonlymphoid tissues of mice treated with LPS, a potent activator of TNFalpha. These data define a novel costimulatory ligand for T cells and suggest that induction of B7h by TNFalpha may function as a mechanism to directly augment recognition of self during inflammation.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3T3 Cells / drug effects
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3T3 Cells / metabolism
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Amino Acid Sequence
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Animals
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Antigen Presentation*
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B-Lymphocytes / drug effects
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B-Lymphocytes / immunology*
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B-Lymphocytes / metabolism
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B7-1 Antigen / chemistry
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B7-1 Antigen / genetics
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Base Sequence
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CHO Cells
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Cricetinae
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Cricetulus
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DNA, Complementary / genetics
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Fibroblasts / drug effects
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Fibroblasts / metabolism
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Gene Expression Regulation / drug effects
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Gene Library
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Genes
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Inducible T-Cell Co-Stimulator Ligand
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Inflammation
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Ligands
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Ligases / metabolism
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Lipopolysaccharides / immunology
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Lymphocyte Activation*
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Lymphocyte Cooperation
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Mice
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Molecular Sequence Data
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Multigene Family
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NF-kappa B / metabolism
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Protein Biosynthesis
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Proteins / genetics
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Proteins / immunology*
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Sequence Alignment
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Sequence Homology, Amino Acid
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Subtraction Technique
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T-Lymphocytes / immunology*
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Tumor Necrosis Factor-alpha / pharmacology*
Substances
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B7-1 Antigen
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DNA, Complementary
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Icosl protein, mouse
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Inducible T-Cell Co-Stimulator Ligand
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Ligands
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Lipopolysaccharides
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NF-kappa B
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Proteins
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Tumor Necrosis Factor-alpha
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Ligases
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guanosine 3',5'-polyphosphate synthetases