Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 365K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Freeman, G. J. Articles by Honjo, T. Search for Related Content PubMed PubMed Citation Articles by Freeman, G. J. Articles by Honjo, T. Pubmed/NCBI databases Gene GEO Profiles HomoloGene OMIM Protein UniGene Substance via MeSH Social Bookmarking                            What's this?

Original Article

^a Department of Adult Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115
^b Genetics Institute, Wyeth-Ayerst Research, Cambridge, Massachusetts 02140
^c Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan
Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.81-75-753-438881-75-753-4371

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 , 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.

Key Words: binding • proliferation inhibition • cytokine secretion inhibition • tissue expression • peripheral tolerance

G.J. Freeman, A.J. Long, and Y. Iwai contributed equally to this work. C.R. Wood and T. Honjo share senior authorship.

© 2000 The Rockefeller University Press

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

• Nagamatsu, T., Schust, D. J., Sugimoto, J., Barrier, B. F. (2009). Human decidual stromal cells suppress cytokine secretion by allogenic CD4+ T cells via PD-1 ligand interactions. Hum Reprod 24: 3160-3171 [Abstract] [Full Text]  
• Castellaneta, A., Sumpter, T. L., Chen, L., Tokita, D., Thomson, A. W. (2009). NOD2 Ligation Subverts IFN-{alpha} Production by Liver Plasmacytoid Dendritic Cells and Inhibits Their T Cell Allostimulatory Activity via B7-H1 Up-Regulation. J. Immunol. 183: 6922-6932 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS