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Blood, 15 July 2004, Vol. 104, No. 2, pp. 453-461. Prepublished online as a Blood First Edition Paper on March 18, 2004; DOI 10.1182/blood-2004-01-0151. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-01-0151v1 104/2/453    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 Godfrey, W. R. Articles by Porter, S. B. Search for Related Content PubMed PubMed Citation Articles by Godfrey, W. R. Articles by Porter, S. B. Related Collections Immunobiology Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY In vitro–expanded human CD4+CD25+ T-regulatory cells can markedly inhibit allogeneic dendritic cell–stimulated MLR cultures Wayne R. Godfrey, Ying G. Ge, Darrin J. Spoden, Bruce L. Levine, Carl H. June, Bruce R. Blazar, and Stephen B. Porter From the Departments of Pediatrics and Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota Cancer Center, Minneapolis; and the Abramson Family Cancer Research Institute, University of Pennsylvania Cancer Center, Philadelphia. CD4+CD25+ T-regulatory (Treg) cells have been shown to critically regulate self- and allograft tolerance in several model systems. Studies of human Treg cells have been restricted by the small number present in peripheral blood and their naturally hypoproliferative state. To better characterize Treg suppressor cell function, we determined methods for the isolation and expansion of these cells. Stringent magnetic microbead-based purification was required for potent suppressor cell line generation. Culture stimulation with cell-sized Dynabeads coated with anti-CD3 and anti-CD28 monoclonal antibodies, CD4+ feeder cells, and interleukin 2, provided for marked expansion in cell number (100-fold), with retention and enhancement of suppressor function. The potent Treg cell lines suppressed proliferation in dendritic cell-driven allo-mixed lymphocyte reaction (MLR) cultures by more than 90%. The Treg-derived suppressor cells functioned early in allo-MLR because expression of activation antigens and accumulation of cytokines was nearly completely prevented. Importantly, cultured Treg cells also suppressed activated and matured dendritic cell-driven responses. These results demonstrate that short-term suppressor cell lines can be generated, and they can express a very potent suppressive activity. This approach will enable more detailed biologic studies of Treg cells and facilitate the evaluation of cultured Treg cells as a novel form of immunosuppressive therapy. (Blood. 2004;104:453-461) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. K. Davies, L. M. Nadler, and E. C. Guinan Expansion of Allospecific Regulatory T Cells After Anergized, Mismatched Bone Marrow Transplantation Science Translational Medicine, October 7, 2009; 1(1): 1ra3 - 1ra3. [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. 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[Abstract] [Full Text] [PDF] W. R. Godfrey, D. J. Spoden, Y. G. Ge, S. R. Baker, B. Liu, B. L. Levine, C. H. June, B. R. Blazar, and S. B. Porter Cord blood CD4+CD25+-derived T regulatory cell lines express FoxP3 protein and manifest potent suppressor function Blood, January 15, 2005; 105(2): 750 - 758. [Abstract] [Full Text] [PDF] P. A. Taylor, A. Panoskaltsis-Mortari, J. M. Swedin, P. J. Lucas, R. E. Gress, B. L. Levine, C. H. June, J. S. Serody, and B. R. Blazar L-Selectinhi but not the L-selectinlo CD4+25+ T-regulatory cells are potent inhibitors of GVHD and BM graft rejection Blood, December 1, 2004; 104(12): 3804 - 3812. [Abstract] [Full Text] [PDF]

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