Abstract
We investigated the in vivo function of the B7 family member B7-H3 (also known as B7RP-2) by gene targeting. B7-H3 inhibited T cell proliferation mediated by antibody to T cell receptor or allogeneic antigen-presenting cells. B7-H3-deficient mice developed more severe airway inflammation than did wild-type mice in conditions in which T helper cells differentiated toward type 1 (T(H)1) rather than type 2 (T(H)2). B7-H3 expression was consistently enhanced by interferon-gamma but suppressed by interleukin 4 in dendritic cells. B7-H3-deficient mice developed experimental autoimmune encephalomyelitis several days earlier than their wild-type littermates, and accumulated higher concentrations of autoantibodies to DNA. Thus, B7-H3 is a negative regulator that preferentially affects T(H)1 responses.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Autoantibodies / immunology
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Autoantibodies / metabolism
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B7 Antigens
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B7-1 Antigen / biosynthesis
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B7-1 Antigen / immunology*
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Dendritic Cells / immunology
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Dendritic Cells / metabolism
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Down-Regulation / immunology
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Encephalomyelitis, Autoimmune, Experimental / immunology
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Encephalomyelitis, Autoimmune, Experimental / pathology
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Flow Cytometry
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Interferon-gamma / immunology
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Interleukin-4 / immunology
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Lymphocyte Activation / immunology
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Lymphocytic choriomeningitis virus / immunology
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Orthomyxoviridae / immunology
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Receptors, Antigen, T-Cell / immunology
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Th1 Cells / immunology*
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Vesicular stomatitis Indiana virus / immunology
Substances
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Autoantibodies
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B7 Antigens
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B7-1 Antigen
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Cd276 protein, mouse
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Receptors, Antigen, T-Cell
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Interleukin-4
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Interferon-gamma