B7-H1 costimulation preferentially enhances CD28-independent T-helper cell function.
B7-H1 is a recently described B7-like molecule that costimulates T-cell growth and cytokine secretion without binding to CD28, cytotoxic T-lymphocyte antigen-4 (CTLA-4), and inducible costimulator (ICOS). In this report, a mouse homologue of human B7-H1 is identified, and its immunologic functions are studied in vitro and in vivo. Mouse B7-H1 shares 69% amino acid homology to the human counterpart. Similar to human B7-H1, mouse B7-H1 can be induced to express on macrophages, T cells, and B cells and to enhance T-cell proliferation and secretion of interleukin-10 (IL-10), interferon-gamma, and granulocyte-macrophage colony-stimulating factor but not IL-2 and IL-4. Furthermore, B7-H1 preferentially costimulates CD4+ T cells independently of CD28 and enhances mixed lymphocyte responses to allogeneic antigens. In contrast to B7-1, expression of B7-H1 on murine P815 tumor cells by transfection fails to increase allogeneic and syngeneic cytolytic T-cell responses in vitro and in vivo. Administration of B7-H1Ig fusion protein, however, enhances keyhole limpet hemocyanin- specific T-cell proliferation and 2,4,6-trinitrophenyl-specific immunoglobulin G2a antibody production. The study thus identifies a unique costimulatory pathway that preferentially affects T-helper cell functions.
Department of Immunology, Mayo Graduate and Medical Schools, Mayo Clinic, Rochester, MN 55905, USA.
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D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000494:pharmacology; D018122:B7-1 Antigen / Q000494:pharmacology*; D051940:B7-2 Antigen; D060890:B7-H1 Antigen; D001798:Blood Proteins; D018106:CD28 Antigens / Q000494:pharmacology*; D003001:Cloning, Molecular; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D060945:Inducible T-Cell Co-Stimulator Ligand; D008024:Ligands; D008562:Membrane Glycoproteins / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D010455:Peptides; D011506:Proteins / Q000494:pharmacology*; D016415:Sequence Alignment; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000187:drug effects* / Q000276:immunology
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D060890:B7-H1 Antigen; D001798:Blood Proteins; C423236:CD274 protein, human; D018106:CD28 Antigens; C497964:CD86 protein, human; C498919:Cd274 protein, mouse; C497965:Cd86 protein, mouse; D016207:Cytokines; C498514:ICOSLG protein, human; C400230:Icosl protein, mouse; D060945:Inducible T-Cell Co-Stimulator Ligand; D008024:Ligands; D008562:Membrane Glycoproteins; D010455:Peptides; D011506:Proteins