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Blood, 1 October 2007, Vol. 110, No. 7, pp. 2501-2510. Prepublished online as a Blood First Edition Paper on June 15, 2007; DOI 10.1182/blood-2007-01-070748. This Article Full Text (PDF) All Versions of this Article: blood-2007-01-070748v1 110/7/2501    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 Vu, M. D. Articles by Li, X. C. Search for Related Content PubMed PubMed Citation Articles by Vu, M. D. Articles by Li, X. C. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 26, 2007 Accepted June 8, 2007 OX40 costimulation turns off Foxp3+ TREGS Minh Diem Vu, Xiang Xiao, Wenda Gao, Nicolas Degauque, Ming Chen, Alexander Kroemer, Nigel Killeen, Naoto Ishii, and Xian Chang Li* Transplant Research Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States Dept of Microbiology and Immunology, University of California San Francisco, San Francisco, CA, United States Dept of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Japan * Corresponding author; email: xli{at}bidmc.harvard.edu. OX40 is a recently identified T cell costimulatory molecule that belongs to the TNF/TNFR superfamily. OX40 can be expressed by activated T effector cells and Foxp3+ TREGS. It is well known that OX40 delivers a potent costimulatory signal to T effector cells, but very little is known about the role of OX40 in regulating the suppressor properties of Foxp3+ TREGS and the de novo generation of new inducible Foxp3+ TREGS from T effector cells. In the present study, we found, by using a newly created Foxp3gfp knockin model, that OX40 was dispensable for the genesis and suppressor functions of naturally arising CD4+Foxp3+ TREGS, but stimulating OX40 on the Foxp3+ TREGS abrogated their ability to suppress T effector cell proliferation, IFN- production, and T effector cell mediated allograft rejection. OX40 costimulation did not significantly affect proliferation and survival of the naturally arising Foxp3+ Tregs, but profoundly inhibited Foxp3 gene expression. Importantly, OX40 costimulation to T effector cells prevented the induction of new inducible Foxp3+ TREGS from T effector cells. Our study identified OX40 as a key negative regulator of Foxp3+ TREGS and may have important clinical implications in models of transplantation and autoimmunity. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: OX40 costimulation and regulatory T cells Jerzy W. Kupiec-Weglinski Blood 2007 110: 2217-2218. [Full Text] [PDF] This article has been cited by other articles: C. E. Ruby, M. A. Yates, D. Hirschhorn-Cymerman, P. Chlebeck, J. D. Wolchok, A. N. Houghton, H. Offner, and A. D. Weinberg Cutting Edge: OX40 Agonists Can Drive Regulatory T Cell Expansion if the Cytokine Milieu Is Right J. Immunol., October 15, 2009; 183(8): 4853 - 4857. [Abstract] [Full Text] [PDF] R. Houot, M. J. Goldstein, H. E. Kohrt, J. H. Myklebust, A. A. Alizadeh, J. T. Lin, J. M. Irish, J. A. Torchia, A. Kolstad, L. Chen, et al. 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