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Blood, 1 January 2004, Vol. 103, No. 1, pp. 177-184. Prepublished online as a Blood First Edition Paper on September 11, 2003; DOI 10.1182/blood-2003-06-2184. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-06-2184v1 103/1/177    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 Wilcox, R. A. Articles by Chen, L. Search for Related Content PubMed PubMed Citation Articles by Wilcox, R. A. Articles by Chen, L. Related Collections Immunobiology Neoplasia Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Ligation of CD137 receptor prevents and reverses established anergy of CD8+ cytolytic T lymphocytes in vivo Ryan A. Wilcox, Koji Tamada, Dallas B. Flies, Gefeng Zhu, Andrei I. Chapoval, Bruce R. Blazar, W. Martin Kast, and Lieping Chen From the Department of Immunology, Mayo Graduate and Medical Schools, Mayo Clinic, Rochester, MN; Cancer Center and Department of Pediatrics, Division of Bone Marrow Transplantation, University of Minnesota, Minneapolis; and Cardinal Bernardin Cancer Center, Loyola University Chicago, Maywood, IL. T-cell anergy is a tolerance mechanism defined as a hyporesponsive status of antigen-specific T cells upon prior antigen encounter and is believed to play a critical role in the evasion of tumor immunity and the amelioration of allogeneic transplant rejection. Molecular mechanisms in controlling T-cell anergy are less known. We show here that administration of an agonistic monoclonal antibody (mAb) to CD137, a member of the tumor necrosis factor receptor superfamily, prevents the induction of CD8+ cytolytic T-lymphocyte (CTL) anergy by soluble antigens. More importantly, CD137 mAb restores the functions of established anergic CTLs upon reencountering their cognate antigen. As a result, infusion of CD137 mAb inhibits progressive tumor growth that is caused by soluble tumor antigen-induced tolerance in a P815R model. CD137 mAb also restores proliferation and effector functions of anergic alloreactive 2C T cells in a bone marrow transplantation model. Our results indicate that ligation of CD137 receptor delivers a regulatory signal for T-cell anergy and implicate manipulation of the CD137 pathway as a new approach to break T-cell tolerance. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Kim, H. J. Kim, K. Park, J. Kim, H.-J. Choi, H. Yagita, S. H. Nam, H. R. Cho, and B. Kwon Costimulatory molecule-targeted immunotherapy of cutaneous graft-versus-host disease Blood, July 15, 2007; 110(2): 776 - 782. [Abstract] [Full Text] [PDF] F. Tsushima, S. Yao, T. Shin, A. Flies, S. Flies, H. Xu, K. Tamada, D. M. Pardoll, and L. Chen Interaction between B7-H1 and PD-1 determines initiation and reversal of T-cell anergy Blood, July 1, 2007; 110(1): 180 - 185. [Abstract] [Full Text] [PDF] Y. Zhu, G. Zhu, L. Luo, A. S. Flies, and L. Chen CD137 stimulation delivers an antigen-independent growth signal for T lymphocytes with memory phenotype Blood, June 1, 2007; 109(11): 4882 - 4889. [Abstract] [Full Text] [PDF] N. Zhang, R. E. Sadun, R. S. Arias, M. L. Flanagan, S. M. Sachsman, Y.-C. Nien, L. A. Khawli, P. Hu, and A. L. Epstein Targeted and Untargeted CD137L Fusion Proteins for the Immunotherapy of Experimental Solid Tumors Clin. 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