Abstract
T cell activation by APCs is regulated by B7-like costimulatory molecules. In this study, we describe a new B7 superfamily member, B7S3, with two differentially spliced isoforms expressed in lymphoid and nonlymphoid tissues. A soluble B7S3-Ig protein bound to professional APC constitutively as well as to activated but not naive T cells. B7S3-Ig treatment greatly inhibited T cell proliferation and IL-2 production. B7S3-Ig also reduced cytokine production by effector T cells. Interestingly, although human genome appears to contain a single-copy B7S3 homolog, the mouse B7S3 gene has 10 relatives within a 2-Mb region constituting a B7S3 gene family. This study identifies B7S3 as a novel negative regulator of T cells, and suggests evolutionarily divergent T cell regulation mechanisms in mammals.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Alternative Splicing / genetics
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Alternative Splicing / immunology
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Animals
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Antigen-Presenting Cells / immunology*
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B7 Antigens
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B7-1 Antigen / genetics
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B7-1 Antigen / immunology*
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B7-1 Antigen / pharmacology
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Cell Proliferation* / drug effects
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Evolution, Molecular
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Gene Expression Regulation / immunology
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Genome, Human / genetics
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Genome, Human / immunology
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Humans
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Immunoglobulins / genetics
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Immunoglobulins / immunology
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Immunoglobulins / pharmacology
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Immunologic Factors / genetics
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Immunologic Factors / immunology*
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Immunologic Factors / pharmacology
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Interleukin-2 / immunology
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Mice
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Multigene Family / genetics
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Multigene Family / immunology
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Organ Specificity / genetics
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Organ Specificity / immunology
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Protein Isoforms / genetics
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Protein Isoforms / immunology
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / immunology
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Recombinant Fusion Proteins / pharmacology
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T-Lymphocytes / immunology*
Substances
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B7 Antigens
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B7-1 Antigen
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Immunoglobulins
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Immunologic Factors
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Interleukin-2
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Protein Isoforms
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Recombinant Fusion Proteins
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Skint2 protein, mouse