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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 (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 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 Related Articles in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 7, 2007 Accepted July 11, 2007 Induction of FOXP3 expression in naive human CD4+FOXP3- T cells by T cell receptor stimulation is TGF-dependent but does not confer a regulatory phenotype Dat Q. Tran, Heather Ramsey, and Ethan M. Shevach* Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD * Corresponding author; email: eshevach{at}niaid.nih.gov. Thymic-derived natural T regulatory cells (nTreg) are important for the induction of self-tolerance and the control of autoimmunity. Murine CD4+CD25-Foxp3- cells can be induced to express Foxp3 following T cell receptor (TCR) activation in the presence of TGF and are phenotypically similar to nTreg. 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 TGF, while high levels of FOXP3 expression could be induced in the presence of TGF. Although FOXP3 expression was stable, the TGF-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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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. 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