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Prepublished online as a Blood First Edition Paper on May 15, 2003; DOI 10.1182/blood-2003-02-0586. This Article Full Text (PDF) All Versions of this Article: 2003-02-0586v1 102/5/1920    most recent Alert me when this article is cited Alert me if a correction is posted 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 Quezada, S. A Articles by Noelle, R. J Search for Related Content PubMed PubMed Citation Articles by Quezada, S. A Articles by Noelle, R. J Social Bookmarking                   What's this? Submitted February 21, 2003 Accepted May 8, 2003 Mechanisms of donor specific transfusion tolerance: pre-emptive induction of clonal T cell exhaustion via indirect presentation Sergio A Quezada, Bruce Fuller, Lamis Z Jarvinen, Mercedes Gonzalez, Bruce R Blazar, Alexander Y Rudensky, Terry B Strom, and Randolph J Noelle* Department of Microbiology & Immunology, Dartmouth Medical School, Lebanon, NH, USA Division of Bone Marrow Transplantation, University of Minnesota, Minneapolis, MN, USA Howard Hughes Institute, University of Washington, Seattle, WA, USA Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA * Corresponding author; email: rjn{at}dartmouth.edu. Induction of transplantation tolerance to alloantigens without general immunosuppression remains as an enduring challenge. Injecting a donor specific transfusion of spleen cells (DST) together with blocking CD154 antibody prior to graft transplantation is an effective way to induce long-lived graft acceptance. Using a novel TCR transgenic model of CD4+ T cell mediated rejection, this study sheds new insights into the cellular basis for enhanced graft survival induced by DST and CD154. The study shows that DST and CD154 induces an early, robust, abortive expansion of the Tg T cells that results in profound anergy. This is contrasted with the more delayed, regional, productive response elicited by an allogeneic graft. Studies show that the induction of tolerance to the allograft induced by DST is mediated by indirect presentation by host APC. Based on these observations, we conclude that DST and CD154 pre-emptively tolerizes the alloreactive T cell compartment to prohibit subsequent responses to the immunogenic allograft. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. M. Miller, T. B. Thornley, T. Pearson, A. J. Kruger, M. Yamazaki, L. D. Shultz, R. M. Welsh, M. A. Brehm, A. A. Rossini, and D. L. Greiner TLR Agonists Prevent the Establishment of Allogeneic Hematopoietic Chimerism in Mice Treated with Costimulation Blockade J. Immunol., May 1, 2009; 182(9): 5547 - 5559. [Abstract] [Full Text] [PDF] J. Kurtz, F. Raval, C. Vallot, J. Der, and M. Sykes CTLA-4 on alloreactive CD4 T cells interacts with recipient CD80/86 to promote tolerance Blood, April 9, 2009; 113(15): 3475 - 3484. [Abstract] [Full Text] [PDF] D. C. Gondek, V. DeVries, E. C. Nowak, L.-F. Lu, K. A. Bennett, Z. A. Scott, and R. J. Noelle Transplantation Survival Is Maintained by Granzyme B+ Regulatory Cells and Adaptive Regulatory T Cells J. Immunol., October 1, 2008; 181(7): 4752 - 4760. [Abstract] [Full Text] [PDF] X. Xiao, A. Kroemer, W. Gao, N. Ishii, G. Demirci, and X. C. 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Quezada, K. Bennett, B. R. Blazar, A. Y. Rudensky, S. Sakaguchi, and R. J. Noelle Analysis of the Underlying Cellular Mechanisms of Anti-CD154-Induced Graft Tolerance: The Interplay of Clonal Anergy and Immune Regulation J. Immunol., July 15, 2005; 175(2): 771 - 779. [Abstract] [Full Text] [PDF] J. Andrassy, S. Kusaka, E. Jankowska-Gan, J. R. Torrealba, L. D. Haynes, B. R. Marthaler, R. C. Tam, B. M.-W. Illigens, N. Anosova, G. Benichou, et al. Tolerance to Noninherited Maternal MHC Antigens in Mice J. Immunol., November 15, 2003; 171(10): 5554 - 5561. [Abstract] [Full Text] [PDF]

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