Characterization of B7S3 as a novel negative regulator of T cells.
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.
Yang
Yang
Y
Department of Immunology, University of Washington, Seattle, WA 98195, USA.
Liu
Xikui K
XK
Nguyen
Thang
T
Bishop
Caroline
C
Graf
Daniel
D
Dong
Chen
C
D017398:Alternative Splicing / Q000235:genetics / Q000276:immunology; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D060887:B7 Antigens; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D019143:Evolution, Molecular; D005786:Gene Expression Regulation / Q000276:immunology; D015894:Genome, Human / Q000235:genetics / Q000276:immunology; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D007155:Immunologic Factors / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D007376:Interleukin-2 / Q000276:immunology; D051379:Mice; D005810:Multigene Family / Q000235:genetics / Q000276:immunology; D009928:Organ Specificity / Q000235:genetics / Q000276:immunology; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology*
D060887:B7 Antigens; D018122:B7-1 Antigen; D007136:Immunoglobulins; D007155:Immunologic Factors; D007376:Interleukin-2; D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins; C519676:Skint2 protein, mouse