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Blood, 15 November 2003, Vol. 102, No. 10, pp. 3815-3821. Prepublished online as a Blood First Edition Paper on July 3, 2003; DOI 10.1182/blood-2002-12-3826. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-12-3826v1 102/10/3815    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 Yvon, E. S. Articles by Brenner, M. K. Search for Related Content PubMed PubMed Citation Articles by Yvon, E. S. Articles by Brenner, M. K. Related Collections Immunobiology Transplantation Signal Transduction Gene Expression Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION Overexpression of the Notch ligand, Jagged-1, induces alloantigen-specific human regulatory T cells Eric S. Yvon, Stephane Vigouroux, Raphael F. Rousseau, Ettore Biagi, Persis Amrolia, Gianpietro Dotti, Hans-Joachim Wagner, and Malcolm K. Brenner From the Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX. Graft-versus-host disease (GVHD) represents one of the major complications of allogeneic hematopoietic stem cell transplantation. Techniques to prevent GVHD have included ex vivo T-cell depletion of the graft or prolonged in vivo immunosuppression. Both reduce the frequency and severity of GVHD but also reduce T-cell-mediated graft-versus-malignancy effect, and increase the risk of infection. A major goal in transplantation is to prevent alloreactivity while preserving activity against tumors and infectious agents. We have used activation of the Notch pathway to try to generate T cells able to specifically regulate alloantigen responses. We used allogeneic Epstein-Barr virus lymphoblastoid B cells (EBV-LCLs) as stimulator cells. Such LCLs are excellent (allo) antigen-presenting cells and can be obtained in large numbers even from donors who have received extensive chemo/radiotherapy. We overexpressed a Notch ligand, Jagged-1, in these cells by adenoviral vector transduction. Stimulation of CD45RA+ naive T cells by Jagged-1 EBV-LCL reduces production of interferon-, interleukin-2, and interleukin-5, but up-regulates transforming growth factor-1 synthesis, consistent with induction of a regulatory T-cell phenotype. Transfer of these T cells to fresh lymphocyte cultures inhibits proliferative and cytotoxic immune responses to the priming alloantigens while sparing responses to third-party stimulator cells. Notch activation in the presence of alloantigen-presenting cells may therefore be a means of inducing specific regulatory T cells while preserving other T-cell functionality. (Blood. 2003;102:3815-3821) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Rutz, M. Janke, N. Kassner, T. Hohnstein, M. Krueger, and A. Scheffold Notch regulates IL-10 production by T helper 1 cells PNAS, March 4, 2008; 105(9): 3497 - 3502. [Abstract] [Full Text] [PDF] N. Asano, T. Watanabe, A. Kitani, I. J. Fuss, and W. Strober Notch1 Signaling and Regulatory T Cell Function J. Immunol., March 1, 2008; 180(5): 2796 - 2804. [Abstract] [Full Text] [PDF] A. Chen, B. Zhao, E. Kieff, J. C. Aster, and F. 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[Abstract] [Full Text] [PDF] A. C. Anderson, E. A. Kitchens, S. W. Chan, C. St. Hill, Y. N. Jan, W. Zhong, and E. A. Robey The Notch Regulator Numb Links the Notch and TCR Signaling Pathways J. Immunol., January 15, 2005; 174(2): 890 - 897. [Abstract] [Full Text] [PDF] S.-i. Tsukumo and K. Yasutomo Notch Governing Mature T Cell Differentiation J. Immunol., December 15, 2004; 173(12): 7109 - 7113. [Abstract] [Full Text] [PDF] S. Vigouroux, E. Yvon, E. Biagi, and M. K. Brenner Antigen-induced regulatory T cells Blood, July 1, 2004; 104(1): 26 - 33. [Abstract] [Full Text] [PDF] T. L. Sumpter and D. S. Wilkes Role of autoimmunity in organ allograft rejection: a focus on immunity to type V collagen in the pathogenesis of lung transplant rejection Am J Physiol Lung Cell Mol Physiol, June 1, 2004; 286(6): L1129 - L1139. [Abstract] [Full Text] [PDF]

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