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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 (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 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 Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 14, 2004 Accepted March 3, 2004 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 Cancer Center, University of Minnesota, Minneapolis, MN, USA Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA, USA * Corresponding author; email: godfr007{at}umn.edu. 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. In order 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 mAbs, CD4+ feeder cells, and IL2, 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-MLR cultures by >90%. The Treg derived suppressor cells functioned early in allo-MLR, as 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. 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