title: B7-H1 is expressed by human endothelial cells and suppresses T cell cytokine synthesis.
abstract: Human endothelial cells (ECs) provide costimulatory signals sufficient to activate resting memory T cells to produce IL-2 and IFN-gamma, at least in part through CD58-CD2 interactions. Recently, the B7-like molecule, B7-H1 (PD-L1), was described and shown to regulate T cell activation; however, there are conflicting reports on whether it stimulates or inhibits T cell cytokine synthesis. B7-H1 is not expressed constitutively by ECs; however, it is rapidly induced by IFN-gamma, and synergistically by IFN-gamma and TNF. In inflamed skin, B7-H1 is expressed by a subset of microvessels, and by keratinocytes, but is barely detectable in normal skin. Blocking the interaction of EC-expressed B7-H1 with its T cell ligand, programmed death-1 (PD-1), using a PD-1-Fc fusion protein, or by blocking B7-H1 expression with morpholino antisense oligonucleotides, augments expression of IL-2 and IFN-gamma, implicating B7-H1 as a negative regulator of cytokine synthesis. However, signaling through PD-1 does not affect induction of the activation markers CD25 or CD69 on T cells, suggesting that its effects are specific to cytokine synthesis. The suppressive effects of B7-H1 on cytokine expression are proportional to the strength of the primary stimulus, allowing for B7-H1 to determine the level of T cell activation in response to ECs. Our results demonstrate that B7-H1 negatively regulates cytokine synthesis in T cells activated by ECs.
authors.affiliation: Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697, USA. lutz@derma.med.uni-erlangen.de
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Mazanet
authors.forename: Christopher C W
authors.initials: CC
authors.lastname: Hughes
mesh_terms: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D018122:B7-1 Antigen / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D060890:B7-H1 Antigen; D001798:Blood Proteins; D002478:Cells, Cultured; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins; D008833:Microcirculation / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D010455:Peptides; D012333:RNA, Messenger / Q000096:biosynthesis; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D012867:Skin / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D017154:Stromal Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013491:Suppressor Factors, Immunologic / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D013997:Time Factors; D014471:Umbilical Veins; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; D001798:Blood Proteins; C423236:CD274 protein, human; D016207:Cytokines; D008562:Membrane Glycoproteins; D010455:Peptides; D012333:RNA, Messenger; D013491:Suppressor Factors, Immunologic