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Blood, 1 August 2004, Vol. 104, No. 3, pp. 895-903. Prepublished online as a Blood First Edition Paper on April 15, 2004; DOI 10.1182/blood-2004-01-0086. This Article Full Text (PDF) All Versions of this Article: 2004-01-0086v1 104/3/895    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 Hoffmann, P. Articles by Edinger, M. Search for Related Content PubMed PubMed Citation Articles by Hoffmann, P. Articles by Edinger, M. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 8, 2004 Accepted April 4, 2004 Large Scale In Vitro Expansion of Polyclonal Human CD4+CD25high Regulatory T Cells Petra Hoffmann, Ruediger Eder, Leoni A Kunz-Schughart, Reinhard Andreesen, and Matthias Edinger* Department of Hematology & Oncology, University Hospital Regensburg, Regensburg, Germany Insitute of Pathology, University Hospital Regensburg, Regensburg, Germany * Corresponding author; email: matthias.edinger{at}klinik.uni-regensburg.de. CD4+CD25+ regulatory T (Treg) cells are pivotal for the maintenance of self-tolerance and their adoptive transfer protects from autoimmune diseases and pathogenic alloresponses after solid organ or bone marrow transplantation in murine model systems. In vitro, human CD4+CD25+ Treg cells display similar phenotypic and functional characteristics as murine CD4+CD25+ Treg cells, namely hyporesponsiveness to TCR stimulation and suppression of CD25- T cells. Thus far, the detailed characterization and potential clinical application of human CD4+CD25+ Treg cells was hampered by their paucity in peripheral blood and the lack of appropriate expansion protocols. Here we describe the up to 40,000-fold expansion of highly purified human CD4+CD25high T cells in vitro through the use of artificial APC for repeated stimulation via CD3 and CD28 in the presence of high dose IL-2. Expanded CD4+CD25high T cells were polyclonal, maintained their phenotype, exceeded the suppressive activity of freshly isolated CD4+CD25high T cells and maintained expression of the lymph node homing receptors CD62L and CCR7. The ability to rapidly expand human CD4+CD25high Treg cells large scale will not only facilitate their further exploration but also accelerate their potential clinical application in T cell-mediated diseases and transplantation medicine. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: 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. M. Wolf, K. Eller, R. Zeiser, C. Durr, U. V. Gerlach, M. Sixt, L. Markut, G. Gastl, A. R. Rosenkranz, and D. Wolf The Sphingosine 1-Phosphate Receptor Agonist FTY720 Potently Inhibits Regulatory T Cell Proliferation In Vitro and In Vivo J. Immunol., September 15, 2009; 183(6): 3751 - 3760. 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