SEARCH:   Advanced

Blood, 1 April 2005, Vol. 105, No. 7, pp. 2845-2851. Prepublished online as a Blood First Edition Paper on December 9, 2004; DOI 10.1182/blood-2004-07-2959. This Article Full Text (PDF) All Versions of this Article: 2004-07-2959v1 105/7/2845    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 Valzasina, B. Articles by Colombo, M. P Search for Related Content PubMed PubMed Citation Articles by Valzasina, B. Articles by Colombo, M. P Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 5, 2004 Accepted November 26, 2004 Triggering of OX40 (CD134) on CD4+CD25+ T cells blocks their inhibitory activity: a novel regulatory role for OX40 and its comparison with GITR Barbara Valzasina, Cristiana Guiducci, Heidrun Dislich, Nigel Killeen, Andrew D Weinberg, and Mario P Colombo* Immunotherapy and Gene Therapy Unit, Department of Experimental Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy Department of Microbiology and Immunology, University of California, San Francisco, CA, USA Earle A. Chiles Research Institute, Robert W. Franz Cancer Research Center, Providence Portland Medical Center, Portland, OR, USA * Corresponding author; email: mcolombo{at}istitutotumori.mi.it. OX40 (CD134) is a member of the TNF receptor family that is transiently expressed on T cells after TCR ligation. Both naive and activated CD4+CD25+ regulatory T cells (T reg) express OX40 but its functional role has not been determined. Since GITR a related TNF receptor family member influences T reg function, we tested whether OX40 might have similar effect. Triggering either GITR or OX40 on T reg using agonist antibodies inhibited their capacity to suppress and restored effector T cell proliferation, IL-2 gene transcription and cytokine production. OX40 abrogation of T reg suppression was confirmed in vivo in a model of GVHD. In a fully allogeneic C57BL/6 >BALB/c bone marrow transplantation, GVHD was lethal unless T reg were co-transferred with the bone marrow and effector T cells. Strikingly, T reg suppression of GVHD was abrogated either by i.p. injection of anti-OX40 or anti-GITR mAbs immediately after transfer, or by in vitro pre-treatment of T reg with the same mAbs before transfer. Cumulatively, the results suggest that in addition to controlling memory T cell numbers, OX40 directly controls T reg cell-mediated suppression. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? 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. Therapeutic effect of CD137 immunomodulation in lymphoma and its enhancement by Treg depletion Blood, October 15, 2009; 114(16): 3431 - 3438. [Abstract] [Full Text] [PDF] S. Piconese, G. Gri, C. Tripodo, S. Musio, A. Gorzanelli, B. Frossi, R. Pedotti, C. E. Pucillo, and M. P. Colombo Mast cells counteract regulatory T-cell suppression through interleukin-6 and OX40/OX40L axis toward Th17-cell differentiation Blood, September 24, 2009; 114(13): 2639 - 2648. [Abstract] [Full Text] [PDF] L. R. Guerin, J. R. Prins, and S. A. Robertson Regulatory T-cells and immune tolerance in pregnancy: a new target for infertility treatment? Hum. Reprod. Update, September 1, 2009; 15(5): 517 - 535. [Abstract] [Full Text] [PDF] 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] A. L. Szymczak-Workman, C. J. Workman, and D. A. A. Vignali Cutting Edge: Regulatory T Cells Do Not Require Stimulation through Their TCR to Suppress J. Immunol., May 1, 2009; 182(9): 5188 - 5192. [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] 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] 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] R. Tao, L. Wang, K. M. Murphy, C. C. Fraser, and W. W. Hancock Regulatory T Cell Expression of Herpesvirus Entry Mediator Suppresses the Function of B and T Lymphocyte Attenuator-Positive Effector T Cells J. Immunol., May 15, 2008; 180(10): 6649 - 6655. [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] M. C. Ruzek, J. S. Waire, D. Hopkins, G. LaCorcia, J. Sullivan, B. L. Roberts, S. M. Richards, S. R. Nahill, J. M. Williams, A. Scaria, et al. Characterization of in vitro antimurine thymocyte globulin-induced regulatory T cells that inhibit graft-versus-host disease in vivo Blood, February 1, 2008; 111(3): 1726 - 1734. [Abstract] [Full Text] [PDF] T. Ramirez-Montagut, A. Chow, D. Hirschhorn-Cymerman, T. H. Terwey, A. A. Kochman, S. Lu, R. C. Miles, S. Sakaguchi, A. N. Houghton, and M. R. M. van den Brink Glucocorticoid-Induced TNF Receptor Family Related Gene Activation Overcomes Tolerance/Ignorance to Melanoma Differentiation Antigens and Enhances Antitumor Immunity. J. Immunol., June 1, 2006; 176(11): 6434 - 6442. [Abstract] [Full Text] [PDF] A. D. Cohen, A. Diab, M.-A. Perales, J. D. Wolchok, G. Rizzuto, T. Merghoub, D. Huggins, C. Liu, M. J. Turk, N. P. Restifo, et al. Agonist Anti-GITR Antibody Enhances Vaccine-Induced CD8+ T-Cell Responses and Tumor Immunity. Cancer Res., May 1, 2006; 66(9): 4904 - 4912. [Abstract] [Full Text] [PDF] S. Murata, B. H. Ladle, P. S. Kim, E. R. Lutz, M. E. Wolpoe, S. E. Ivie, H. M. Smith, T. D. Armstrong, L. A. Emens, E. M. Jaffee, et al. OX40 Costimulation Synergizes with GM-CSF Whole-Cell Vaccination to Overcome Established CD8+ T Cell Tolerance to an Endogenous Tumor Antigen J. Immunol., January 15, 2006; 176(2): 974 - 983. [Abstract] [Full Text] [PDF]

	Copyright © 2004 by American Society of Hematology         Online ISSN: 1528-0020