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Blood, 15 September 2008, Vol. 112, No. 6, pp. 2554-2562. Prepublished online as a Blood First Edition Paper on July 3, 2008; DOI 10.1182/blood-2008-04-152041. This Article Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2008-04-152041v1 112/6/2554    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 Tu, W. Articles by Lewis, D. B. Search for Related Content PubMed PubMed Citation Articles by Tu, W. Articles by Lewis, D. B. Related Collections Related Articles in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 15, 2008 Accepted June 23, 2008 Efficient generation of human alloantigen-specific CD4+ regulatory T cells from naive precursors by CD40-activated B cells Wenwei Tu*, Yu-Lung Lau, Jian Zheng, Yinping Liu, Ping-Lung Chan, Huawei Mao, Kira Dionis, Pascal Schneider, and David B. Lewis Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, China Pediatrics, Stanford University, Stanford, California, United States Biochemistry, University of Lausanne, Epalinges, Switzerland * Corresponding author; email: wwtu{at}hkucc.hku.hk. CD4+CD25+Foxp3+ regulatory T cells (Treg) play an important role in the induction and maintenance of immune tolerance. Although adoptive transfer of bulk populations of Treg can prevent or treat T-cell-mediated inflammatory diseases and transplant allograft rejection in animal models, optimal Treg immunotherapy in humans would ideally use antigen-specific rather than polyclonal Treg for greater specificity of regulation and avoidance of general suppression. However, no robust approaches have been reported for the generation of human antigen-specific Treg at a practical scale for clinical use. Here, we report a simple and cost-effective novel method to rapidly induce and expand large numbers of functional human alloantigen-specific Treg from antigenically-naive precursors in vitro using allogeneic non-transformed B cells as stimulators. By this approach naive CD4+CD25- T cells could be expanded 8-fold into alloantigen-specific Treg after 3 weeks of culture without any exogenous cytokines. The induced alloantigen-specific Treg were CD45RO+CCR7- memory cells, and had a CD4high, CD25+, Foxp3+ and CD62L (L-selectin)+ phenotype. Although these CD4highCD25+Foxp3+ alloantigen-specific Treg had no cytotoxic capacity, their suppressive function was cell-cell contact dependent and partially relied on CTLA-4 expression. This approach may accelerate the clinical application of Treg-based immunotherapy in transplantation and autoimmune diseases. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Articles in Blood Online: Activated human B cells: stimulatory or tolerogenic antigen-presenting cells? Alexander Shimabukuro-Vornhagen, Eisei Kondo, Tanja Liebig, and Michael von Bergwelt-Baildon Blood 2009 114: 746-747. [Full Text] [PDF] Response: Stimulatory or tolerogenic role of CD40-activated B cells depends on the strength of the activation to T cells Wenwei Tu, Jian Zheng, Yinping Liu, and Yu-Lung Lau Blood 2009 114: 747-748. [Full Text] [PDF] This article has been cited by other articles: H. Mao, W. Tu, G. Qin, H. K. W. Law, S. F. Sia, P.-L. Chan, Y. Liu, K.-T. Lam, J. Zheng, M. Peiris, et al. Influenza Virus Directly Infects Human Natural Killer Cells and Induces Cell Apoptosis J. Virol., September 15, 2009; 83(18): 9215 - 9222. [Abstract] [Full Text] [PDF] L. C. Chen, J. C. Delgado, P. E. Jensen, and X. Chen Direct Expansion of Human Allospecific FoxP3+CD4+ Regulatory T Cells with Allogeneic B Cells for Therapeutic Application J. Immunol., September 15, 2009; 183(6): 4094 - 4102. [Abstract] [Full Text] [PDF] J. Zheng, Y. Liu, G. Qin, P.-L. Chan, H. Mao, K.-T. Lam, D. B. Lewis, Y.-L. Lau, and W. Tu Efficient Induction and Expansion of Human Alloantigen-Specific CD8 Regulatory T Cells from Naive Precursors by CD40-Activated B Cells J. Immunol., September 15, 2009; 183(6): 3742 - 3750. [Abstract] [Full Text] [PDF] A. Shimabukuro-Vornhagen, E. Kondo, T. Liebig, and M. von Bergwelt-Baildon Activated human B cells: stimulatory or tolerogenic antigen-presenting cells? Blood, July 16, 2009; 114(3): 746 - 747. [Full Text] [PDF] W. Tu, J. Zheng, Y. Liu, and Y.-L. Lau Response: Stimulatory or tolerogenic role of CD40-activated B cells depends on the strength of the activation to T cells Blood, July 16, 2009; 114(3): 747 - 748. [Full Text] [PDF]

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