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Blood, 15 October 2007, Vol. 110, No. 8, pp. 2983-2990. Prepublished online as a Blood First Edition Paper on July 20, 2007; DOI 10.1182/blood-2007-06-094656. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-06-094656v1 110/8/2983    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 Tran, D. Q. Articles by Shevach, E. M. Search for Related Content PubMed PubMed Citation Articles by Tran, D. Q. Articles by Shevach, E. M. Related Collections Immunobiology Gene Expression Related Articles in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Induction of FOXP3 expression in naive human CD4+FOXP3– T cells by T-cell receptor stimulation is transforming growth factor-ß–dependent but does not confer a regulatory phenotype Dat Q. Tran1, Heather Ramsey1, and Ethan M. Shevach1 1 Laboratory of Immunology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD Thymic-derived natural T-regulatory cells (nTregs) are important for the induction of self-tolerance and the control of autoimmunity. Murine CD4+CD25–Foxp3– cells can be induced to express Foxp3 after T-cell receptor (TCR) activation in the presence of transforming growth factor ß (TGFß) and are phenotypically similar to nTregs. Some studies have suggested that TCR stimulation of human CD4+CD25– cells results in the induction of transient expression of FOXP3, but that the induced cells lack a regulatory phenotype. We demonstrate here that TCR stimulation alone was insufficient to induce FOXP3 expression in the absence of TGFß, whereas high levels of FOXP3 expression could be induced in the presence of TGFß. Although FOXP3 expression was stable, the TGFß-induced FOXP3+ T cells were neither anergic nor suppressive and produced high levels of effector cytokines. These results suggest that even high levels of FOXP3 expression are insufficient to define a human CD4+ T cell as a T-regulatory cell. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Articles in Blood Online: Defense of the clone: antibody 259D effectively labels human FOXP3 in a variety of applications Bridget C. Fox, Paola A. Bignone, Philip J. Brown, and Alison H. Banham Blood 2008 111: 3897-3899. 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[Abstract] [Full Text] [PDF] A. W. Mailloux and M. R. I. Young NK-Dependent Increases in CCL22 Secretion Selectively Recruits Regulatory T Cells to the Tumor Microenvironment J. Immunol., March 1, 2009; 182(5): 2753 - 2765. [Abstract] [Full Text] [PDF] E. F. de Zoeten, I. Lee, L. Wang, C. Chen, G. Ge, A. D. Wells, W. W. Hancock, and E. Ozkaynak Foxp3 Processing by Proprotein Convertases and Control of Regulatory T Cell Function J. Biol. Chem., February 27, 2009; 284(9): 5709 - 5716. [Abstract] [Full Text] [PDF] Y. H. Kim, B. K. Choi, H. S. Oh, W. J. Kang, R. S. Mittler, and B. S. Kwon Mechanisms involved in synergistic anticancer effects of anti-4-1BB and cyclophosphamide therapy Mol. Cancer Ther., February 1, 2009; 8(2): 469 - 478. [Abstract] [Full Text] [PDF] M. Kleinewietfeld, M. Starke, D. Di Mitri, G. Borsellino, L. Battistini, O. Rotzschke, and K. Falk CD49d provides access to "untouched" human Foxp3+ Treg free of contaminating effector cells Blood, January 22, 2009; 113(4): 827 - 836. [Abstract] [Full Text] [PDF] G. Lal, N. Zhang, W. van der Touw, Y. Ding, W. Ju, E. P. Bottinger, St. P. Reid, D. E. Levy, and J. S. Bromberg Epigenetic Regulation of Foxp3 Expression in Regulatory T Cells by DNA Methylation J. Immunol., January 1, 2009; 182(1): 259 - 273. [Abstract] [Full Text] [PDF] D. S. Game, X. Cao, and S. Jiang Regulatory T Cells: The Cunning Fox and Its Clinical Application Sci. Signal., December 23, 2008; 1(51): mr3 - mr3. [Abstract] [Full Text] [PDF] C. Vogtenhuber, M. J. O'Shaughnessy, D. A. A. Vignali, and B. R. Blazar Outgrowth of CD4low/negCD25+ T Cells with Suppressor Function in CD4+CD25+ T Cell Cultures upon Polyclonal Stimulation Ex Vivo J. Immunol., December 15, 2008; 181(12): 8767 - 8775. [Abstract] [Full Text] [PDF] F. Flores-Borja, E. C. Jury, C. Mauri, and M. R. Ehrenstein Defects in CTLA-4 are associated with abnormal regulatory T cell function in rheumatoid arthritis PNAS, December 9, 2008; 105(49): 19396 - 19401. [Abstract] [Full Text] [PDF] E. Bardel, F. Larousserie, P. Charlot-Rabiega, A. Coulomb-L'Hermine, and O. Devergne Human CD4+CD25+Foxp3+ Regulatory T Cells Do Not Constitutively Express IL-35 J. Immunol., November 15, 2008; 181(10): 6898 - 6905. [Abstract] [Full Text] [PDF] Y. Miyahara, K. Odunsi, W. Chen, G. Peng, J. Matsuzaki, and R.-F. Wang Generation and regulation of human CD4+ IL-17-producing T cells in ovarian cancer PNAS, October 7, 2008; 105(40): 15505 - 15510. [Abstract] [Full Text] [PDF] J. Andersson, D. Q. Tran, M. Pesu, T. S. Davidson, H. Ramsey, J. J. O'Shea, and E. M. Shevach CD4+FoxP3+ regulatory T cells confer infectious tolerance in a TGF-{beta}-dependent manner J. Exp. Med., September 1, 2008; 205(9): 1975 - 1981. [Abstract] [Full Text] [PDF] M. Kasprzycka, Q. Zhang, A. Witkiewicz, M. Marzec, M. Potoczek, X. Liu, H. Y. Wang, M. Milone, S. Basu, J. Mauger, et al. {gamma}c-Signaling Cytokines Induce a Regulatory T Cell Phenotype in Malignant CD4+ T Lymphocytes J. Immunol., August 15, 2008; 181(4): 2506 - 2512. [Abstract] [Full Text] [PDF] B. Kavanagh, S. O'Brien, D. Lee, Y. Hou, V. Weinberg, B. Rini, J. P. Allison, E. J. Small, and L. Fong CTLA4 blockade expands FoxP3+ regulatory and activated effector CD4+ T cells in a dose-dependent fashion Blood, August 15, 2008; 112(4): 1175 - 1183. [Abstract] [Full Text] [PDF] C. Brinster and E. M. Shevach Costimulatory effects of IL-1 on the expansion/differentiation of CD4+CD25+Foxp3+ and CD4+CD25+Foxp3- T cells J. Leukoc. Biol., August 1, 2008; 84(2): 480 - 487. [Abstract] [Full Text] [PDF] A. Fragale, L. Gabriele, E. Stellacci, P. Borghi, E. Perrotti, R. Ilari, A. Lanciotti, A. L. Remoli, M. Venditti, F. Belardelli, et al. IFN Regulatory Factor-1 Negatively Regulates CD4+CD25+ Regulatory T Cell Differentiation by Repressing Foxp3 Expression J. Immunol., August 1, 2008; 181(3): 1673 - 1682. [Abstract] [Full Text] [PDF] Y. Zheng, C. N. Manzotti, F. Burke, L. Dussably, O. Qureshi, L. S. K. Walker, and D. M. Sansom Acquisition of Suppressive Function by Activated Human CD4+CD25- T Cells Is Associated with the Expression of CTLA-4 Not FoxP3 J. Immunol., August 1, 2008; 181(3): 1683 - 1691. [Abstract] [Full Text] [PDF] N. D. L. Savage, T. de Boer, K. V. Walburg, S. A. Joosten, K. van Meijgaarden, A. Geluk, and T. H. M. Ottenhoff Human Anti-Inflammatory Macrophages Induce Foxp3+GITR+CD25+ Regulatory T Cells, Which Suppress via Membrane-Bound TGF{beta}-1 J. Immunol., August 1, 2008; 181(3): 2220 - 2226. [Abstract] [Full Text] [PDF] M. Nagar, H. Vernitsky, Y. Cohen, D. Dominissini, Y. Berkun, G. Rechavi, N. Amariglio, and I. Goldstein Epigenetic inheritance of DNA methylation limits activation-induced expression of FOXP3 in conventional human CD25-CD4+ T cells Int. Immunol., August 1, 2008; 20(8): 1041 - 1055. [Abstract] [Full Text] [PDF] I Heier, K Malmstrom, A S Pelkonen, L P Malmberg, M Kajosaari, M Turpeinen, H Lindahl, P Brandtzaeg, F L Jahnsen, and M J Makela Bronchial response pattern of antigen presenting cells and regulatory T cells in children less than 2 years of age Thorax, August 1, 2008; 63(8): 703 - 709. [Abstract] [Full Text] [PDF] Y L Woo, J Sterling, R Crawford, S H van der Burg, N Coleman, and M Stanley FOXP3 immunohistochemistry on formalin-fixed paraffin-embedded tissue: poor correlation between different antibodies J. Clin. Pathol., August 1, 2008; 61(8): 969 - 971. [Abstract] [Full Text] [PDF] E. S. Yolcu, X. Gu, C. Lacelle, H. Zhao, L. Bandura-Morgan, N. Askenasy, and H. Shirwan Induction of Tolerance to Cardiac Allografts Using Donor Splenocytes Engineered to Display on Their Surface an Exogenous Fas Ligand Protein J. Immunol., July 15, 2008; 181(2): 931 - 939. [Abstract] [Full Text] [PDF] C. Scotta, M. Soligo, C. Camperio, and E. Piccolella FOXP3 Induced by CD28/B7 Interaction Regulates CD25 and Anergic Phenotype in Human CD4+CD25- T Lymphocytes J. Immunol., July 15, 2008; 181(2): 1025 - 1033. [Abstract] [Full Text] [PDF] A. Serra, S. Nuti, S. Tavarini, C. Sammicheli, D. Rosa, G. Saletti, E. Soldaini, S. Abrignani, and A. Wack Coligation of the Hepatitis C Virus Receptor CD81 with CD28 Primes Naive T Lymphocytes to Acquire Type 2 Effector Function J. Immunol., July 1, 2008; 181(1): 174 - 185. [Abstract] [Full Text] [PDF] H. Liu and C. Rohowsky-Kochan Regulation of IL-17 in Human CCR6+ Effector Memory T Cells J. Immunol., June 15, 2008; 180(12): 7948 - 7957. [Abstract] [Full Text] [PDF] C. Grant, U. Oh, K. Yao, Y. Yamano, and S. Jacobson Dysregulation of TGF-{beta} signaling and regulatory and effector T-cell function in virus-induced neuroinflammatory disease Blood, June 15, 2008; 111(12): 5601 - 5609. [Abstract] [Full Text] [PDF] S. Sauer, L. Bruno, A. Hertweck, D. Finlay, M. Leleu, M. Spivakov, Z. A. Knight, B. S. Cobb, D. Cantrell, E. O'Connor, et al. T cell receptor signaling controls Foxp3 expression via PI3K, Akt, and mTOR PNAS, June 3, 2008; 105(22): 7797 - 7802. [Abstract] [Full Text] [PDF] B. C. Fox, P. A. Bignone, P. J. Brown, and A. H. Banham Defense of the clone: antibody 259D effectively labels human FOXP3 in a variety of applications Blood, April 1, 2008; 111(7): 3897 - 3899. [Full Text] [PDF] L. Passerini, S. E. Allan, M. Battaglia, S. Di Nunzio, A. N. Alstad, M. K. Levings, M. G. Roncarolo, and R. Bacchetta STAT5-signaling cytokines regulate the expression of FOXP3 in CD4+CD25+ regulatory T cells and CD4+CD25- effector T cells Int. Immunol., March 1, 2008; 20(3): 421 - 431. [Abstract] [Full Text] [PDF] L. C. Ndhlovu, C. P. Loo, G. Spotts, D. F. Nixon, and F. M. Hecht FOXP3 expressing CD127lo CD4+ T cells inversely correlate with CD38+ CD8+ T cell activation levels in primary HIV-1 infection J. Leukoc. Biol., February 1, 2008; 83(2): 254 - 262. [Abstract] [Full Text] [PDF] L. Das and A. D. Levine TGF-{beta} Inhibits IL-2 Production and Promotes Cell Cycle Arrest in TCR-Activated Effector/Memory T Cells in the Presence of Sustained TCR Signal Transduction J. Immunol., February 1, 2008; 180(3): 1490 - 1498. [Abstract] [Full Text] [PDF] V. Pillai and N. J. Karandikar Attack on the clones? Human FOXP3 detection by PCH101, 236A/E7, 206D, and 259D reveals 259D as the outlier with lower sensitivity Blood, January 1, 2008; 111(1): 463 - 464. [Full Text] [PDF] D. Q. Tran and E. M. Shevach Response: Anti human FOXP3 mAb PCH101 stains activated human naive T cells nonspecifically Blood, January 1, 2008; 111(1): 464 - 466. [Full Text] [PDF]

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