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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 (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 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 Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 25, 2006 Accepted August 26, 2006 In vitro expanded donor alloantigen-specific CD4+CD25+ regulatory T cells promote experimental transplantation tolerance Dela Golshayan, Shuiping Jiang, Julia Tsang, Marina I Garin, Christian Mottet, and Robert I Lechler* Department of Immunology, Imperial College, Hammersmith Hospital, London, UK Department of Nephrology and Transplantation, King's College London School of Medicine, London, UK Sir William Dunn School of Pathology, University of Oxford, Oxford, UK * Corresponding author; email: robert.lechler{at}kcl.ac.uk. CD4+CD25+ T cells (Tregs) play a critical role in the induction and maintenance of peripheral immune tolerance. In experimental transplantation models where tolerance was induced, donor-specific Tregs 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 Tregs 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 Tregs of CBA mice (H2k). Compared to fresh Tregs, the cell lines maintained their characteristic phenotype, suppressive function and homing capacities in vivo. When cotransferred with naive CD4+CD25- effector T cells into thymectomised and T cell-depleted CBA mice grafted with a CBK (H2k+Kb) skin, the expanded Tregs 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 Tregs significantly delayed CBK skin graft rejection without any other immunosuppression. Taken together these data suggest that in vitro generated tailored Tregs could be considered as a therapeutic tool to promote donor-specific transplantation 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. 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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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