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Blood, 1 July 2007, Vol. 110, No. 1, pp. 186-192. Prepublished online as a Blood First Edition Paper on March 28, 2007; DOI 10.1182/blood-2006-12-062422. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-12-062422v1 110/1/186    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Goldberg, M. V. Articles by Drake, C. G. Search for Related Content PubMed PubMed Citation Articles by Goldberg, M. V. Articles by Drake, C. G. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Role of PD-1 and its ligand, B7-H1, in early fate decisions of CD8 T cells Monica V. Goldberg1, Charles H. Maris1, Edward L. Hipkiss1, Andrew S. Flies1, Lijie Zhen2, Rubin M. Tuder2, Joseph F. Grosso1, Timothy J. Harris1, Derese Getnet1, Katharine A. Whartenby1, Dirk G. Brockstedt3, Thomas W. Dubensky, Jr3, Lieping Chen1, Drew M. Pardoll1, and Charles G. Drake1 1 Department of Oncology, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD; 2 Department of Pathology, Johns Hopkins University, Baltimore, MD; and 3 Cerus Corporation, Concord, CA Expression of the PD-1 receptor on T cells has been shown to provide an important inhibitory signal that down-modulates peripheral effector responses in normal tissues and tumors. Furthermore, PD-1 up-regulation on chronically activated T cells can maintain them in a partially reversible inactive state. The function of PD-1 in the very early stages of T-cell response to antigen in vivo has not been fully explored. In this study, we evaluate the role of PD-1 and its 2 B7 family ligands, B7-H1 (PD-L1) and B7-DC (PD-L2), in early fate decisions of CD8 T cells. We show that CD8 T cells specific for influenza hemagglutinin (HA) expressed as a self-antigen become functionally tolerized and express high levels of surface PD-1 by the time of their first cell division. Blockade of PD-1 or B7-H1, but not B7-DC, at the time of self-antigen encounter mitigates tolerance induction and results in CD8 T-cell differentiation into functional cytolytic T lymphocytes (CTLs). These findings demonstrate that, in addition to modulating effector functions in the periphery, B7-H1:PD-1 interactions regulate early T-cell–fate decisions. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Calbo, H. Delagreverie, C. Arnoult, F.-J. Authier, F. Tron, and O. Boyer Functional Tolerance of CD8+ T Cells Induced by Muscle-Specific Antigen Expression J. Immunol., July 1, 2008; 181(1): 408 - 417. [Abstract] [Full Text] [PDF] R. Berger, R. Rotem-Yehudar, G. Slama, S. Landes, A. Kneller, M. Leiba, M. Koren-Michowitz, A. Shimoni, and A. Nagler Phase I Safety and Pharmacokinetic Study of CT-011, a Humanized Antibody Interacting with PD-1, in Patients with Advanced Hematologic Malignancies Clin. Cancer Res., May 15, 2008; 14(10): 3044 - 3051. [Abstract] [Full Text] [PDF] J. R. Lukens, M. W. Cruise, M. G. Lassen, and Y. S. Hahn Blockade of PD-1/B7-H1 Interaction Restores Effector CD8+ T Cell Responses in a Hepatitis C Virus Core Murine Model J. Immunol., April 1, 2008; 180(7): 4875 - 4884. [Abstract] [Full Text] [PDF] T. Azuma, S. Yao, G. Zhu, A. S. Flies, S. J. Flies, and L. Chen B7-H1 is a ubiquitous antiapoptotic receptor on cancer cells Blood, April 1, 2008; 111(7): 3635 - 3643. [Abstract] [Full Text] [PDF] K. L. Alderson, Q. Zhou, V. Berner, D. E. C. Wilkins, J. M. Weiss, B. R. Blazar, L. A. Welniak, R. H. Wiltrout, D. Redelman, and W. J. Murphy Regulatory and Conventional CD4+ T Cells Show Differential Effects Correlating with PD-1 and B7-H1 Expression after Immunotherapy J. Immunol., March 1, 2008; 180(5): 2981 - 2988. [Abstract] [Full Text] [PDF] R. P. Singh, A. La Cava, and B. H. Hahn pConsensus Peptide Induces Tolerogenic CD8+ T Cells in Lupus-Prone (NZB x NZW)F1 Mice by Differentially Regulating Foxp3 and PD1 Molecules J. Immunol., February 15, 2008; 180(4): 2069 - 2080. [Abstract] [Full Text] [PDF] P. E. Zarek, C.-T. Huang, E. R. Lutz, J. Kowalski, M. R. Horton, J. Linden, C. G. Drake, and J. D. Powell A2A receptor signaling promotes peripheral tolerance by inducing T-cell anergy and the generation of adaptive regulatory T cells Blood, January 1, 2008; 111(1): 251 - 259. [Abstract] [Full Text] [PDF]

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