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Engagement of the Pd-1 Immunoinhibitory Receptor by a Novel B7 Family Member Leads to Negative Regulation of Lymphocyte Activation
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. Engageme...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2000
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193311/ https://www.ncbi.nlm.nih.gov/pubmed/11015443 |
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author | Freeman, Gordon J. Long, Andrew J. Iwai, Yoshiko Bourque, Karen Chernova, Tatyana Nishimura, Hiroyuki Fitz, Lori J. Malenkovich, Nelly Okazaki, Taku Byrne, Michael C. Horton, Heidi F. Fouser, Lynette Carter, Laura Ling, Vincent Bowman, Michael R. Carreno, Beatriz M. Collins, Mary Wood, Clive R. Honjo, Tasuku |
author_facet | Freeman, Gordon J. Long, Andrew J. Iwai, Yoshiko Bourque, Karen Chernova, Tatyana Nishimura, Hiroyuki Fitz, Lori J. Malenkovich, Nelly Okazaki, Taku Byrne, Michael C. Horton, Heidi F. Fouser, Lynette Carter, Laura Ling, Vincent Bowman, Michael R. Carreno, Beatriz M. Collins, Mary Wood, Clive R. Honjo, Tasuku |
author_sort | Freeman, Gordon J. |
collection | PubMed |
description | 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 γ, 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. |
format | Text |
id | pubmed-2193311 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2000 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21933112008-04-16 Engagement of the Pd-1 Immunoinhibitory Receptor by a Novel B7 Family Member Leads to Negative Regulation of Lymphocyte Activation Freeman, Gordon J. Long, Andrew J. Iwai, Yoshiko Bourque, Karen Chernova, Tatyana Nishimura, Hiroyuki Fitz, Lori J. Malenkovich, Nelly Okazaki, Taku Byrne, Michael C. Horton, Heidi F. Fouser, Lynette Carter, Laura Ling, Vincent Bowman, Michael R. Carreno, Beatriz M. Collins, Mary Wood, Clive R. Honjo, Tasuku J Exp Med Original Article 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 γ, 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. The Rockefeller University Press 2000-10-02 /pmc/articles/PMC2193311/ /pubmed/11015443 Text en © 2000 The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Original Article Freeman, Gordon J. Long, Andrew J. Iwai, Yoshiko Bourque, Karen Chernova, Tatyana Nishimura, Hiroyuki Fitz, Lori J. Malenkovich, Nelly Okazaki, Taku Byrne, Michael C. Horton, Heidi F. Fouser, Lynette Carter, Laura Ling, Vincent Bowman, Michael R. Carreno, Beatriz M. Collins, Mary Wood, Clive R. Honjo, Tasuku Engagement of the Pd-1 Immunoinhibitory Receptor by a Novel B7 Family Member Leads to Negative Regulation of Lymphocyte Activation |
title | Engagement of the Pd-1 Immunoinhibitory Receptor by a Novel B7 Family Member Leads to Negative Regulation of Lymphocyte Activation |
title_full | Engagement of the Pd-1 Immunoinhibitory Receptor by a Novel B7 Family Member Leads to Negative Regulation of Lymphocyte Activation |
title_fullStr | Engagement of the Pd-1 Immunoinhibitory Receptor by a Novel B7 Family Member Leads to Negative Regulation of Lymphocyte Activation |
title_full_unstemmed | Engagement of the Pd-1 Immunoinhibitory Receptor by a Novel B7 Family Member Leads to Negative Regulation of Lymphocyte Activation |
title_short | Engagement of the Pd-1 Immunoinhibitory Receptor by a Novel B7 Family Member Leads to Negative Regulation of Lymphocyte Activation |
title_sort | engagement of the pd-1 immunoinhibitory receptor by a novel b7 family member leads to negative regulation of lymphocyte activation |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193311/ https://www.ncbi.nlm.nih.gov/pubmed/11015443 |
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