SEARCH:   Advanced

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 Immunotherapy Immunobiology 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: M. Esquerre, B. Tauzin, M. Guiraud, S. Muller, A. Saoudi, and S. Valitutti Human regulatory T cells inhibit polarization of T helper cells toward antigen-presenting cells via a TGF-{beta}-dependent mechanism PNAS, February 19, 2008; 105(7): 2550 - 2555. [Abstract] [Full Text] [PDF] R. Aricha, T. Feferman, S. Fuchs, and M. C. Souroujon Ex Vivo Generated Regulatory T Cells Modulate Experimental Autoimmune Myasthenia Gravis J. Immunol., February 15, 2008; 180(4): 2132 - 2139. [Abstract] [Full Text] [PDF] A. K. Antons, R. Wang, K. Oswald-Richter, M. Tseng, C. W. Arendt, S. A. Kalams, and D. Unutmaz Naive Precursors of Human Regulatory T Cells Require FoxP3 for Suppression and Are Susceptible to HIV Infection J. Immunol., January 15, 2008; 180(2): 764 - 773. [Abstract] [Full Text] [PDF] K. G. Elpek, E. S. Yolcu, D. D. H. Franke, C. Lacelle, R.-H. Schabowsky, and H. Shirwan Ex Vivo Expansion of CD4+CD25+FoxP3+ T Regulatory Cells Based on Synergy between IL-2 and 4-1BB Signaling J. Immunol., December 1, 2007; 179(11): 7295 - 7304. [Abstract] [Full Text] [PDF] M. P. Bell, P. A. Svingen, M. K. Rahman, Y. Xiong, and W. A. Faubion Jr. Forkhead Box P3 Regulates TLR10 Expression in Human T Regulatory Cells J. Immunol., August 1, 2007; 179(3): 1893 - 1900. [Abstract] [Full Text] [PDF] X. Valencia, C. Yarboro, G. Illei, and P. E. Lipsky Deficient CD4+CD25high T Regulatory Cell Function in Patients with Active Systemic Lupus Erythematosus J. Immunol., February 15, 2007; 178(4): 2579 - 2588. [Abstract] [Full Text] [PDF] L. Strauss, T. L. Whiteside, A. Knights, C. Bergmann, A. Knuth, and A. Zippelius Selective Survival of Naturally Occurring Human CD4+CD25+Foxp3+ Regulatory T Cells Cultured with Rapamycin J. Immunol., January 1, 2007; 178(1): 320 - 329. [Abstract] [Full Text] [PDF] M. Battaglia, A. Stabilini, B. Migliavacca, J. Horejs-Hoeck, T. Kaupper, and M.-G. Roncarolo Rapamycin Promotes Expansion of Functional CD4+CD25+FOXP3+ Regulatory T Cells of Both Healthy Subjects and Type 1 Diabetic Patients J. Immunol., December 15, 2006; 177(12): 8338 - 8347. [Abstract] [Full Text] [PDF] C. A. Lawson, A. K. Brown, V. Bejarano, S. H. Douglas, C. H. Burgoyne, A. S. Greenstein, A. W. Boylston, P. Emery, F. Ponchel, and J. D. Isaacs Early rheumatoid arthritis is associated with a deficit in the CD4+CD25high regulatory T cell population in peripheral blood Rheumatology, October 1, 2006; 45(10): 1210 - 1217. [Abstract] [Full Text] [PDF] E. Zorn and J. Ritz Studying Human Regulatory T Cells In vivo. Clin. Cancer Res., September 15, 2006; 12(18): 5265 - 5267. [Full Text] [PDF] X. Valencia, G. Stephens, R. Goldbach-Mansky, M. Wilson, E. M. Shevach, and P. E. Lipsky TNF downmodulates the function of human CD4+CD25hi T-regulatory cells Blood, July 1, 2006; 108(1): 253 - 261. [Abstract] [Full Text] [PDF] D. Adeegbe, A. L. Bayer, R. B. Levy, and T. R. Malek Cutting Edge: Allogeneic CD4+CD25+Foxp3+ T Regulatory Cells Suppress Autoimmunity while Establishing Transplantation Tolerance. J. Immunol., June 15, 2006; 176(12): 7149 - 7153. [Abstract] [Full Text] [PDF] F. Fandrich Induction of tolerance in clinical organ transplantation Nephrol. Dial. Transplant., May 1, 2006; 21(5): 1170 - 1173. [Full Text] [PDF] S. G. Zheng, L. Meng, J. H. Wang, M. Watanabe, M. L. Barr, D. V. Cramer, J. D. Gray, and D. A. Horwitz Transfer of regulatory T cells generated ex vivo modifies graft rejection through induction of tolerogenic CD4+CD25+ cells in the recipient Int. Immunol., February 1, 2006; 18(2): 279 - 289. [Abstract] [Full Text] [PDF] A. Trenado, M. Sudres, Q. Tang, S. Maury, F. Charlotte, S. Gregoire, M. Bonyhadi, D. Klatzmann, B. L. Salomon, and J. L. Cohen Ex Vivo-Expanded CD4+CD25+ Immunoregulatory T Cells Prevent Graft-versus-Host-Disease by Inhibiting Activation/Differentiation of Pathogenic T Cells J. Immunol., January 15, 2006; 176(2): 1266 - 1273. [Abstract] [Full Text] [PDF] M. Firan, S. Dhillon, P. Estess, and M. H. Siegelman Suppressor activity and potency among regulatory T cells is discriminated by functionally active CD44 Blood, January 15, 2006; 107(2): 619 - 627. [Abstract] [Full Text] [PDF] J. Harnaha, J. Machen, M. Wright, R. Lakomy, A. Styche, M. Trucco, S. Makaroun, and N. Giannoukakis Interleukin-7 Is a Survival Factor for CD4+ CD25+ T-Cells and Is Expressed by Diabetes-Suppressive Dendritic Cells Diabetes, January 1, 2006; 55(1): 158 - 170. [Abstract] [Full Text] [PDF] A. J. M. van Oosterhout and N. Bloksma Regulatory T-lymphocytes in asthma Eur. Respir. J., November 1, 2005; 26(5): 918 - 932. [Abstract] [Full Text] [PDF] L. Li, W. R. Godfrey, S. B. Porter, Y. Ge, C. H. June, B. R. Blazar, and V. A. Boussiotis CD4+CD25+ regulatory T-cell lines from human cord blood have functional and molecular properties of T-cell anergy Blood, November 1, 2005; 106(9): 3068 - 3073. [Abstract] [Full Text] [PDF] T. Hiura, H. Kagamu, S. Miura, A. Ishida, H. Tanaka, J. Tanaka, F. Gejyo, and H. Yoshizawa Both Regulatory T Cells and Antitumor Effector T Cells Are Primed in the Same Draining Lymph Nodes during Tumor Progression J. Immunol., October 15, 2005; 175(8): 5058 - 5066. [Abstract] [Full Text] [PDF] C. Dercamp, K. Chemin, C. Caux, G. Trinchieri, and A. P. Vicari Distinct and Overlapping Roles of Interleukin-10 and CD25+ Regulatory T Cells in the Inhibition of Antitumor CD8 T-Cell Responses Cancer Res., September 15, 2005; 65(18): 8479 - 8486. [Abstract] [Full Text] [PDF] H. J. P. M. Koenen, E. Fasse, and I. Joosten CD27/CFSE-Based Ex Vivo Selection of Highly Suppressive Alloantigen-Specific Human Regulatory T Cells J. Immunol., June 15, 2005; 174(12): 7573 - 7583. [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]

	Blood Online is supported in part by Genentech BioOncology and Biogen Idec
	Copyright © 2004 by American Society of Hematology         Online ISSN: 1528-0020