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This Article Full Text Full Text (PDF) 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 Taylor, P. A. Articles by Blazar, B. R. Search for Related Content PubMed PubMed Citation Articles by Taylor, P. A. Articles by Blazar, B. R. Related Collections Transplantation Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 June 2002, Vol. 99, No. 12, pp. 4601-4609 TRANSPLANTATION Tolerance induction of alloreactive T cells via ex vivo blockade of the CD40:CD40L costimulatory pathway results in the generation of a potent immune regulatory cell Patricia A. Taylor, Thea M. Friedman, Robert Korngold, Randolph J. Noelle, and Bruce R. Blazar From the University of Minnesota Cancer Center and Department of Pediatrics, Division of Bone Marrow Transplantation, Minneapolis; Kimmel Cancer Institute, Thomas Jefferson Medical College, Philadelphia, PA; Department of Microbiology, Dartmouth Medical College, Hanover, NH. We previously reported that ex vivo blockade of the CD40:CD40L costimulatory pathway in primary mixed lymphocyte reaction cultures resulted in profound in vitro secondary hyporesponsiveness and 30-fold or greater protection from graft-versus-host-disease (GVHD) lethality. Present studies demonstrate that tolerance induction via costimulatory blockade also results in the generation of a potent immunoregulatory cell that inhibits both naive and primed alloresponses. The immunoregulatory capacity was dependent upon cell-to-cell contact that prevented the full activation of the naive or primed cells. The inhibitory effect of tolerized cells did not preclude the response of naive T cells to nominal protein antigen if antigen was present at high concentration. However, under suboptimal antigen concentration, nonspecific inhibition of responses occurred. The tolerized regulatory cell population maintained a polyclonal T-cell receptor V repertoire that was broader than in control primed cultures. These data, the first to demonstrate that tolerance induction via CD40:CD40L costimulatory blockade results in potent regulatory function, are relevant to bone-marrow and solid-organ transplantation. The generation of potent immunoregulatory capacity during tolerization via CD40:CD40L blockade provides a fail-safe mechanism to control alloreactive T cells that may have escaped tolerization. These potent regulatory cells may be clinically exploitable for the treatment and prevention of GVHD or autoimmunity. © 2002 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. K. Davies, L. M. Nadler, and E. C. Guinan Expansion of Allospecific Regulatory T Cells After Anergized, Mismatched Bone Marrow Transplantation Science Translational Medicine, October 7, 2009; 1(1): 1ra3 - 1ra3. [Abstract] [Full Text] [PDF] M. Suzuki, X. Zheng, X. Zhang, M. Li, C. Vladau, T. E. Ichim, H. Sun, L. R. Min, B. Garcia, and W.-P. Min Novel Vaccination for Allergy through Gene Silencing of CD40 Using Small Interfering RNA J. Immunol., June 15, 2008; 180(12): 8461 - 8469. [Abstract] [Full Text] [PDF] S. Mielke, R. Nunes, K. Rezvani, V. S. Fellowes, A. Venne, S. R. Solomon, Y. Fan, E. Gostick, D. A. Price, C. Scotto, et al. 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	Copyright © 2002 by American Society of Hematology         Online ISSN: 1528-0020