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Blood, 15 January 2005, Vol. 105, No. 2, pp. 750-758. Prepublished online as a Blood First Edition Paper on September 16, 2004; DOI 10.1182/blood-2004-06-2467. This Article Full Text (PDF) All Versions of this Article: 2004-06-2467v1 105/2/750    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 June 29, 2004 Accepted September 6, 2004 Cord blood CD4+CD25+ derived T regulatory cell lines express FoxP3 protein and manifest potent suppressor function Wayne R Godfrey*, Darrin J Spoden, Ying G Ge, Seth R Baker, Baoling Liu, Bruce L Levine, Carl H June, Bruce R Blazar, and Stephen B Porter Departments of Pediatrics and Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota Cancer Center, Minneapolis, MN, USA Abramson Family Cancer Research Institute, University of Pennsylvania Cancer Center, Philadelphia, PA, USA * Corresponding author; email: wgodfrey{at}dendreon.com. CD4+CD25+ T regulatory (Treg) cells have been shown to critically regulate self and allograft tolerance in mice. Studies of human Treg have been hindered by low numbers present in peripheral blood and difficult purification. We found that cord blood was a superior source for Treg isolation and cell line generation compared to adult blood. Cord blood CD4+CD25+ cells were readily purified, and generated cell lines that consistently exhibited potent suppressor activity, with >95% suppression of allogeneic MLR (29/30 donors). Cultured Treg cells blocked cytokine accumulation in MLR, with a less robust inhibition of chemokine production. These cell lines uniformly expressed CD25, CD62L, CCR7, CD27, and intracellular CTLA4. FoxP3 protein, but not mRNA, was specifically expressed. Upon re-stimulation with anti-CD3/CD28 beads, the cultured Treg produced minimal cytokines (IL2, IFN-gamma, and IL10), and preferentially expressed TGF-beta latency associated protein. Cytokine production however, was restored to normal levels by re-stimulation with PMA/ionomycin. Cord blood derived cultured suppressor cell function was predominantly independent of IL10 and TGF-beta. These results demonstrate cord blood contains a significant number of Treg precursor cells, capable of potent suppressor function after culture activation. Banked cord blood specimens may serve as a readily available source of Treg for immunotherapy. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. J. Haller, C. H. Wasserfall, K. M. McGrail, M. Cintron, T. M. Brusko, J. R. Wingard, S. S. Kelly, J. J. Shuster, M. A. Atkinson, and D. A. Schatz Autologous Umbilical Cord Blood Transfusion in Very Young Children With Type 1 Diabetes Diabetes Care, November 1, 2009; 32(11): 2041 - 2046. [Abstract] [Full Text] [PDF] D. Q. Tran, J. Andersson, D. Hardwick, L. Bebris, G. G. Illei, and E. M. Shevach Selective expression of latency-associated peptide (LAP) and IL-1 receptor type I/II (CD121a/CD121b) on activated human FOXP3+ regulatory T cells allows for their purification from expansion cultures Blood, May 21, 2009; 113(21): 5125 - 5133. [Abstract] [Full Text] [PDF] J. F. Hutton, T. Gargett, T. J. Sadlon, S. Bresatz, C. Y. Brown, H. Zola, M. F. Shannon, R. J. D'Andrea, and S. C. Barry Development of CD4+CD25+FoxP3+ regulatory T cells from cord blood hematopoietic progenitor cells J. Leukoc. Biol., March 1, 2009; 85(3): 445 - 451. [Abstract] [Full Text] [PDF] J. J. A. Coenen, H. J. P. M. Koenen, E. van Rijssen, L. B. Hilbrands, and I. Joosten Rapamycin, and not cyclosporin A, preserves the highly suppressive CD27+ subset of human CD4+CD25+ regulatory T cells Blood, February 1, 2006; 107(3): 1018 - 1023. [Abstract] [Full Text] [PDF] E. Biagi, R. Rousseau, E. Yvon, M. Schwartz, G. Dotti, A. Foster, D. Havlik-Cooper, B. Grilley, A. Gee, K. Baker, et al. Responses to Human CD40 Ligand/Human Interleukin-2 Autologous Cell Vaccine in Patients with B-Cell Chronic Lymphocytic Leukemia Clin. Cancer Res., October 1, 2005; 11(19): 6916 - 6923. [Abstract] [Full Text] [PDF] B. R Blazar and W. J Murphy Bone marrow transplantation and approaches to avoid graft-versus-host disease (GVHD) Phil Trans R Soc B, September 29, 2005; 360(1461): 1747 - 1767. [Abstract] [Full Text] [PDF]

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