Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation
| Autor: | Lynette A. Fouser, Mary Collins, Michael R Bowman, Tasuku Honjo, Heidi F. Horton, Vincent Ling, Laura L. Carter, Beatriz M. Carreno, Andrew J. Long, Nelly Malenkovich, Karen Bourque, Lori Fitz, Yoshiko Iwai, Tatyana Chernova, Clive Wood, Taku Okazaki, Gordon J. Freeman, Michael C. Byrne, Hiroyuki Nishimura |
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| Rok vydání: | 2000 |
| Předmět: |
DNA
Complementary binding CD3 Complex medicine.medical_treatment T cell T-Lymphocytes Immunology Molecular Sequence Data Programmed Cell Death 1 Receptor Antigen-Presenting Cells Gene Expression Lymphocyte proliferation Biology Ligands 03 medical and health sciences Mice 0302 clinical medicine CD28 Antigens Antigens CD medicine Immunology and Allergy Animals Humans Interferon gamma IL-2 receptor Amino Acid Sequence cytokine secretion inhibition Antigen-presenting cell 030304 developmental biology 0303 health sciences Membrane Glycoproteins Base Sequence ZAP70 Peripheral tolerance peripheral tolerance proliferation inhibition Cell biology Cytokine medicine.anatomical_structure tissue expression Antigens Surface B7-1 Antigen Original Article B7-2 Antigen Apoptosis Regulatory Proteins Cell Division 030215 immunology medicine.drug Signal Transduction |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 0022-1007 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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