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Prepublished online as a Blood First Edition Paper on July 3, 2003; DOI 10.1182/blood-2002-12-3826. This Article 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 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 Social Bookmarking                   What's this? Submitted December 18, 2002 Accepted June 12, 2003 Over expression 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* Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA * Corresponding author; email: mbrenner{at}bcm.tmc.edu. 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 whilst 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 EBV-lymphoblastoid B cells (EBV-LCL) 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 reduces production of interferon-g, interleukin-2 and interleukin-5, but upregulates Transforming Growth Factor-b1 synthesis, consistent with induction of a regulatory T cell phenotype. Transfer of these cells to fresh lymphocyte cultures inhibits proliferative and cytotoxic immune responses to the priming alloantigens whilst 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 whilst preserving other T cell functionality. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M.-T. Huang, Y.-S. Dai, Y.-B. Chou, Y.-H. Juan, C.-C. Wang, and B.-L. Chiang Regulatory T Cells Negatively Regulate Neovasculature of Airway Remodeling via DLL4-Notch Signaling J. Immunol., October 1, 2009; 183(7): 4745 - 4754. [Abstract] [Full Text] [PDF] E. Yvon, M. Del Vecchio, B. Savoldo, V. Hoyos, A. Dutour, A. Anichini, G. Dotti, and M. K. Brenner Immunotherapy of Metastatic Melanoma Using Genetically Engineered GD2-Specific T cells Clin. Cancer Res., September 15, 2009; 15(18): 5852 - 5860. [Abstract] [Full Text] [PDF] X.-L. Zhang, J. Peng, J.-Z. Sun, J.-J. Liu, C.-S. Guo, Z.-G. Wang, Y. Yu, Y. Shi, P. Qin, S.-G. Li, et al. 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