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Blood, 1 March 2005, Vol. 105, No. 5, pp. 2206-2213. Prepublished online as a Blood First Edition Paper on November 2, 2004; DOI 10.1182/blood-2004-06-2080. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: 2004-06-2080v1 105/5/2206    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 Kim, J. Articles by Kwon, B. Search for Related Content PubMed PubMed Citation Articles by Kim, J. Articles by Kwon, B. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 2, 2004 Accepted October 20, 2004 4-1BB (CD137) stimulation inhibits chronic graft-versus-host disease by inducing activation-induced cell death of donor CD4+ T cells Juyang Kim, Woon S Choi, Soojin La, Jae-Hee Suh, Byoung-Sam Kim, Hong R Cho, Byoung S Kwon, and Byungsuk Kwon* Immunomodulation Research Center, University of Ulsan, Ulsan, Korea, Republic of Department of Pathology, Ulsan University Hospital, Ulsan, Korea, Republic of * Corresponding author; email: bkwon{at}mail.ulsan.ac.kr. 4-1BB, a member of the TNF receptor superfamily, is a costimulator for activated T cells. Previous studies have established that treatment with agonistic anti-4-BB monoclonal antibody (3H3) is effective in reversing the progression of spontaneous systemic lupus erythematosus. Its therapeutic effect is mediated by suppression of autoantibody production. In this report, we show that a single injection of 3H3 blocks chronic graft-versus-host disease (cGVHD) in the parent-into-F1 model. In particular, donor CD4+ T cells are rapidly eliminated from host spleens by activation-induced cell death after 4-1BB triggering. Since donor CD4+ T cells are required for the development of cGVHD, and 3H3-mediated inhibition of autoantibody production occurs without donor CD8+ T cells, 3H3 blocks cGVHD by preventing alloreactive donor CD4+ T cells from activating host B cells. Importantly, 3H3 treatment can reverse the progression of advanced cGVHD. Our findings indicate that agonistic anti-4-1BB monoclonal antibody has potential as an immunotherapeutic agent for preventing and treating cGVHD. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S.-W. Lee, S. Salek-Ardakani, R. S. Mittler, and M. Croft Hypercostimulation through 4-1BB Distorts Homeostasis of Immune Cells J. Immunol., June 1, 2009; 182(11): 6753 - 6762. [Abstract] [Full Text] [PDF] J. Kim, K. Park, H. J. Kim, J. Kim, H.-A Kim, D. Jung, H. J. Kim, H.-J. Choi, S.-Y. Choi, K. W. Seo, et al. Breaking of CD8+ T Cell Tolerance through In Vivo Ligation of CD40 Results in Inhibition of Chronic Graft-versus-Host Disease and Complete Donor Cell Engraftment J. Immunol., November 15, 2008; 181(10): 7380 - 7389. [Abstract] [Full Text] [PDF] D.-H. Kim, W.-S. Chang, Y.-S. Lee, K.-A Lee, Y.-K. Kim, B. S. Kwon, and C.-Y. Kang 4-1BB Engagement Costimulates NKT Cell Activation and Exacerbates NKT Cell Ligand-Induced Airway Hyperresponsiveness and Inflammation J. Immunol., February 15, 2008; 180(4): 2062 - 2068. [Abstract] [Full Text] [PDF] J. Kim, H. J. Kim, K. Park, J. Kim, H.-J. Choi, H. Yagita, S. H. Nam, H. R. Cho, and B. Kwon Costimulatory molecule-targeted immunotherapy of cutaneous graft-versus-host disease Blood, July 15, 2007; 110(2): 776 - 782. [Abstract] [Full Text] [PDF] S.-W. Lee, Y. Park, A. Song, H. Cheroutre, B. S. Kwon, and M. Croft Functional Dichotomy between OX40 and 4-1BB in Modulating Effector CD8 T Cell Responses J. Immunol., October 1, 2006; 177(7): 4464 - 4472. [Abstract] [Full Text] [PDF] Y. Sun, S. E. Blink, W. Liu, Y. Lee, B. Chen, J. Solway, J. Weinstock, L. Chen, and Y.-X. Fu Inhibition of Th2-Mediated Allergic Airway Inflammatory Disease by CD137 Costimulation J. Immunol., July 15, 2006; 177(2): 814 - 821. [Abstract] [Full Text] [PDF] J. Kim, W. S. Choi, H. Kang, H. J. Kim, J.-H. Suh, S. Sakaguchi, and B. Kwon Conversion of Alloantigen-Specific CD8+ T Cell Anergy to CD8+ T Cell Priming through In Vivo Ligation of Glucocorticoid-Induced TNF Receptor J. Immunol., May 1, 2006; 176(9): 5223 - 5231. [Abstract] [Full Text] [PDF] A. Fukushima, T. Yamaguchi, W. Ishida, K. Fukata, R. S. Mittler, H. Yagita, and H. Ueno Engagement of 4-1BB Inhibits the Development of Experimental Allergic Conjunctivitis in Mice J. Immunol., October 15, 2005; 175(8): 4897 - 4903. [Abstract] [Full Text] [PDF]

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