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Blood, 15 July 2007, Vol. 110, No. 2, pp. 776-782. Prepublished online as a Blood First Edition Paper on March 15, 2007; DOI 10.1182/blood-2006-08-043612. This Article Full Text (PDF) All Versions of this Article: blood-2006-08-043612v1 110/2/776    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 August 25, 2006 Accepted March 9, 2007 Costimulatory molecule-targeted immunotherapy of cutaneous graft-versus-host disease Juyang Kim, Hye J Kim, Keunhee Park, Jiyoung Kim, Hye-Jeong Choi, Hideo Yagita, Seok H Nam, Hong R Cho, and Byungsuk Kwon* Department of Biological Science, University of Ulsan, Ulsan, Korea, Republic of Department of Pathology, Ulsan University Hospital, Ulsan, Korea, Republic of Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan Department of Biological Science, Ajou University, Suwon, Korea, Republic of Department of Surgery & Biomedical Research Center, Ulsan University Hospital, Ulsan, Korea, Republic of * Corresponding author; email: bkwon{at}mail.ulsan.ac.kr. Chronic graft-versus-host disease (cGVHD) is an increasingly frequent complication of allogeneic stem cell transplantation. Current therapies for cGVHD reduce symptoms but are not cures. The B10.D2Balb/c (H-2d) minor histocompatibility antigen-mismatched model, which reflects clinical and pathological symptoms of human cGVHD, was used in this study. We demonstrated that a single injection of an agonistic monoclonal antibody (mAb) against CD137, a member of the tumor necrosis factor receptor superfamily, reverses skin fibrosis, ulceration and alopecia, a dominant feature of cGVHD (cutaneous GVHD), ultimately improving general health conditions. The reversal is associated with markedly reduced CD4+ T cell cytokines and increased apoptosis of donor CD4+ T cells. The Fas pathway is required for ameliorating cutaneous GVHD by anti-CD137 mAb. Taken together, these data indicate that the anti-CD137 mAb has a therapeutic effect on cutaneous GVHD by removing donor CD4+ T cells that cause cutaneous GVHD. Thus, our study demonstrates an agonistic mAb, specific for a costimulatory molecule, as a possible target for therapeutic intervention in cutaneous GVHD. 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]

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