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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 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 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 Vu, M. D. Articles by Chang Li, X. Search for Related Content PubMed PubMed Citation Articles by Vu, M. D. Articles by Chang Li, X. Related Collections Immunobiology Signal Transduction Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY OX40 costimulation turns off Foxp3+ Tregs Minh Diem Vu1, Xiang Xiao1, Wenda Gao1, Nicolas Degauque1, Ming Chen1, Alexander Kroemer1, Nigel Killeen2, Naoto Ishii3, and Xian Chang Li1 1 Harvard Medical School, Transplant Research Center, Beth Israel Deaconess Medical Center, Boston, MA; 2 Department of Microbiology and Immunology, University of California San Francisco; 3 Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Japan OX40 is a recently identified T-cell costimulatory molecule that belongs to the TNF/TNFR superfamily. OX40 can be expressed by both 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: D. Hirschhorn-Cymerman, G. A. Rizzuto, T. Merghoub, A. D. Cohen, F. Avogadri, A. M. Lesokhin, A. D. Weinberg, J. D. Wolchok, and A. N. Houghton OX40 engagement and chemotherapy combination provides potent antitumor immunity with concomitant regulatory T cell apoptosis J. Exp. Med., May 11, 2009; 206(5): 1103 - 1116. [Abstract] [Full Text] [PDF] R. Houot and R. Levy T-cell modulation combined with intratumoral CpG cures lymphoma in a mouse model without the need for chemotherapy Blood, April 9, 2009; 113(15): 3546 - 3552. [Abstract] [Full Text] [PDF] P. Krause, M. Bruckner, C. Uermosi, E. Singer, M. Groettrup, and D. F. Legler Prostaglandin E2 enhances T-cell proliferation by inducing the costimulatory molecules OX40L, CD70, and 4-1BBL on dendritic cells Blood, March 12, 2009; 113(11): 2451 - 2460. [Abstract] [Full Text] [PDF] C. E. Ruby and A. D. Weinberg OX40-Enhanced Tumor Rejection and Effector T Cell Differentiation Decreases with Age J. Immunol., February 1, 2009; 182(3): 1481 - 1489. [Abstract] [Full Text] [PDF] B. Wilde, S. Dolff, X. Cai, C. Specker, J. Becker, M. Totsch, U. Costabel, J. Durig, A. Kribben, J. W. C. Tervaert, et al. CD4+CD25+ T-cell populations expressing CD134 and GITR are associated with disease activity in patients with Wegener's granulomatosis Nephrol. Dial. Transplant., January 1, 2009; 24(1): 161 - 171. [Abstract] [Full Text] [PDF] B. E. Burrell, G. Lu, X. C. Li, and D. K. Bishop OX40 Costimulation Prevents Allograft Acceptance Induced by CD40-CD40L Blockade J. Immunol., January 1, 2009; 182(1): 379 - 390. [Abstract] [Full Text] [PDF] M. J. Gough, C. E. Ruby, W. L. Redmond, B. Dhungel, A. Brown, and A. D. Weinberg OX40 Agonist Therapy Enhances CD8 Infiltration and Decreases Immune Suppression in the Tumor Cancer Res., July 1, 2008; 68(13): 5206 - 5215. [Abstract] [Full Text] [PDF] A. Joetham, S. Matsubara, M. Okamoto, K. Takeda, N. Miyahara, A. Dakhama, and E. W. Gelfand Plasticity of Regulatory T Cells: Subversion of Suppressive Function and Conversion to Enhancement of Lung Allergic Responses J. Immunol., June 1, 2008; 180(11): 7117 - 7124. [Abstract] [Full Text] [PDF] S. Piconese, B. Valzasina, and M. P. Colombo OX40 triggering blocks suppression by regulatory T cells and facilitates tumor rejection J. Exp. Med., April 14, 2008; 205(4): 825 - 839. [Abstract] [Full Text] [PDF]

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