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Blood, 15 January 2007, Vol. 109, No. 2, pp. 827-835. Prepublished online as a Blood First Edition Paper on September 26, 2006; DOI 10.1182/blood-2006-05-025460. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-05-025460v1 109/2/827    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 Golshayan, D. Articles by Lechler, R. I. Search for Related Content PubMed PubMed Citation Articles by Golshayan, D. Articles by Lechler, R. I. Related Collections Immunobiology Transplantation Free Research Articles Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION In vitro–expanded donor alloantigen–specific CD4+CD25+ regulatory T cells promote experimental transplantation tolerance Dela Golshayan1, Shuiping Jiang1,2, Julia Tsang1,2, Marina I. Garin1,2, Christian Mottet3, and Robert I. Lechler1,2, 1 Department of Immunology, Imperial College, Hammersmith Hospital, London, United Kingdom; 2 Department of Nephrology and Transplantation, King's College London School of Medicine at Guy's King's College and St Thomas' Hospitals, London, United Kingdom; 3 Sir William Dunn School of Pathology, University of Oxford, United Kingdom CD4+CD25+ regulatory T (Treg) cells play a critical role in the induction and maintenance of peripheral immune tolerance. In experimental transplantation models in which tolerance was induced, donor-specific Treg cells could be identified that were capable of transferring the tolerant state to naive animals. Furthermore, these cells appeared to have indirect allospecificity for donor antigens. Here we show that in vivo alloresponses can be regulated by donor alloantigen-specific Treg cells selected and expanded in vitro. Using autologous dendritic cells pulsed with an allopeptide from H2-Kb, we generated and expanded T-cell lines from purified Treg cells of CBA mice (H2k). Compared with fresh Treg cells, the cell lines maintained their characteristic phenotype, suppressive function, and homing capacities in vivo. When cotransferred with naive CD4+CD25– effector T cells after thymectomy and T-cell depletion in CBA mice that received CBK (H2k+Kb) skin grafts, the expanded Treg cells preferentially accumulated in the graft-draining lymph nodes and within the graft while preventing CBK but not third-party B10.A (H2k+Dd) skin graft rejection. In wild-type CBA, these donor-specific Treg cells significantly delayed CBK skin graft rejection without any other immunosuppression. Taken together, these data suggest that in vitro–generated tailored Treg cells could be considered a therapeutic tool to promote donor-specific transplant tolerance. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Wang, T. W. J. Huizinga, and R. E. M. Toes De Novo Generation and Enhanced Suppression of Human CD4+CD25+ Regulatory T Cells by Retinoic Acid J. Immunol., September 15, 2009; 183(6): 4119 - 4126. [Abstract] [Full Text] [PDF] K. E. Webster, S. Walters, R. E. Kohler, T. Mrkvan, O. Boyman, C. D. Surh, S. T. Grey, and J. Sprent In vivo expansion of T reg cells with IL-2-mAb complexes: induction of resistance to EAE and long-term acceptance of islet allografts without immunosuppression J. Exp. Med., April 13, 2009; 206(4): 751 - 760. [Abstract] [Full Text] [PDF] J. F. Hutton, T. Gargett, T. J. Sadlon, S. Bresatz, C. Y. Brown, H. Zola, M. F. Shannon, R. J. D'Andrea, and S. C. Barry Development of CD4+CD25+FoxP3+ regulatory T cells from cord blood hematopoietic progenitor cells J. Leukoc. Biol., March 1, 2009; 85(3): 445 - 451. [Abstract] [Full Text] [PDF] N. D. Verma, K. M. Plain, M. Nomura, G. T. Tran, C. Robinson, R. Boyd, S. J. Hodgkinson, and B. M. Hall CD4+CD25+ T cells alloactivated ex vivo by IL-2 or IL-4 become potent alloantigen-specific inhibitors of rejection with different phenotypes, suggesting separate pathways of activation by Th1 and Th2 responses Blood, January 8, 2009; 113(2): 479 - 487. [Abstract] [Full Text] [PDF] C. Vogtenhuber, M. J. O'Shaughnessy, D. A. A. Vignali, and B. R. Blazar Outgrowth of CD4low/negCD25+ T Cells with Suppressor Function in CD4+CD25+ T Cell Cultures upon Polyclonal Stimulation Ex Vivo J. Immunol., December 15, 2008; 181(12): 8767 - 8775. [Abstract] [Full Text] [PDF] W. Tu, Y.-L. Lau, J. Zheng, Y. Liu, P.-L. Chan, H. Mao, K. Dionis, P. Schneider, and D. B. Lewis Efficient generation of human alloantigen-specific CD4+ regulatory T cells from naive precursors by CD40-activated B cells Blood, September 15, 2008; 112(6): 2554 - 2562. [Abstract] [Full Text] [PDF] N. Wan, H. Dai, T. Wang, Y. Moore, X. X. Zheng, and Z. Dai Bystander Central Memory but Not Effector Memory CD8+ T Cells Suppress Allograft Rejection J. Immunol., January 1, 2008; 180(1): 113 - 121. [Abstract] [Full Text] [PDF]

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