Engagement of the Pd-1 Immunoinhibitory Receptor by a Novel B7 Family Member Leads to Negative Regulation of Lymphocyte Activation

• Gordon J. Freeman

  aDepartment of Adult Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115

• Andrew J. Long

  bGenetics Institute, Wyeth-Ayerst Research, Cambridge, Massachusetts 02140

• Yoshiko Iwai

  cDepartment of Medical Chemistry, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan

• Karen Bourque

  bGenetics Institute, Wyeth-Ayerst Research, Cambridge, Massachusetts 02140

• Tatyana Chernova

  aDepartment of Adult Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115

• Hiroyuki Nishimura

  cDepartment of Medical Chemistry, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan

• Lori J. Fitz

  bGenetics Institute, Wyeth-Ayerst Research, Cambridge, Massachusetts 02140

• Nelly Malenkovich

  aDepartment of Adult Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115

• Taku Okazaki

  cDepartment of Medical Chemistry, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan

• Michael C. Byrne

  bGenetics Institute, Wyeth-Ayerst Research, Cambridge, Massachusetts 02140

• Heidi F. Horton

  bGenetics Institute, Wyeth-Ayerst Research, Cambridge, Massachusetts 02140

• Lynette Fouser

  bGenetics Institute, Wyeth-Ayerst Research, Cambridge, Massachusetts 02140

• Laura Carter

  bGenetics Institute, Wyeth-Ayerst Research, Cambridge, Massachusetts 02140

• Vincent Ling

  bGenetics Institute, Wyeth-Ayerst Research, Cambridge, Massachusetts 02140

• Michael R. Bowman

  bGenetics Institute, Wyeth-Ayerst Research, Cambridge, Massachusetts 02140

• Beatriz M. Carreno

  bGenetics Institute, Wyeth-Ayerst Research, Cambridge, Massachusetts 02140

• Mary Collins

  bGenetics Institute, Wyeth-Ayerst Research, Cambridge, Massachusetts 02140

• Clive R. Wood

  bGenetics Institute, Wyeth-Ayerst Research, Cambridge, Massachusetts 02140

• Tasuku Honjo

  cDepartment of Medical Chemistry, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan

抄録

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.

収録刊行物

• The Journal of Experimental Medicine

  The Journal of Experimental Medicine 192 (7), 1027-1034, 2000-10-02

  Rockefeller University Press

キーワード

• Immunology
• Immunology and Allergy

詳細情報

• CRID: 1362262943943605888
• NII論文ID: 30017415579
• DOI: 10.1084/jem.192.7.1027
• ISSN: 15409538
• ISSN: 00221007
• ISSN: http://id.crossref.org/issn/00221007
• Web Site: https://rupress.org/jem/article-pdf/192/7/1027/1699884/001387.pdf
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  • CiNii Articles