Abstract
PD-1 is an immunoinhibitory receptor expressed by activated T cells, B cells, and myeloid cells. Mice deficient in PD-1 exhibit a breakdown of peripheral tolerance and demonstrate multiple autoimmune features. We report here that the ligand of PD-1 (PD-L1) is a member of the B7 gene family. Engagement of PD-1 by PD-L1 leads to the inhibition of T cell receptor-mediated lymphocyte proliferation and cytokine secretion. In addition, PD-1 signaling can inhibit at least suboptimal levels of CD28-mediated costimulation. PD-L1 is expressed by antigen-presenting cells, including human peripheral blood monocytes stimulated with interferon gamma, and activated human and murine dendritic cells. In addition, PD-L1 is expressed in nonlymphoid tissues such as heart and lung. The relative levels of inhibitory PD-L1 and costimulatory B7-1/B7-2 signals on antigen-presenting cells may determine the extent of T cell activation and consequently the threshold between tolerance and autoimmunity. PD-L1 expression on nonlymphoid tissues and its potential interaction with PD-1 may subsequently determine the extent of immune responses at sites of inflammation.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Antigen-Presenting Cells / immunology
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Antigens, CD / classification
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Antigens, CD / genetics
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Antigens, CD / immunology*
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Antigens, Surface / genetics
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Antigens, Surface / immunology*
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Antigens, Surface / metabolism
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Apoptosis Regulatory Proteins
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B7-1 Antigen / classification
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B7-1 Antigen / genetics
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B7-1 Antigen / immunology*
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B7-2 Antigen
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Base Sequence
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CD28 Antigens / immunology
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CD3 Complex / immunology
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Cell Division
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DNA, Complementary
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Gene Expression
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Humans
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Ligands
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Membrane Glycoproteins / classification
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / immunology*
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Mice
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Molecular Sequence Data
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Programmed Cell Death 1 Receptor
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Signal Transduction / immunology
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T-Lymphocytes / cytology
Substances
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Antigens, CD
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Antigens, Surface
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Apoptosis Regulatory Proteins
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B7-1 Antigen
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B7-2 Antigen
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CD28 Antigens
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CD3 Complex
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CD86 protein, human
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Cd86 protein, mouse
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DNA, Complementary
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Ligands
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Membrane Glycoproteins
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PDCD1 protein, human
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Pdcd1 protein, mouse
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Programmed Cell Death 1 Receptor
Associated data
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GENBANK/AF233516
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GENBANK/AF233517