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Blood, 15 November 2007, Vol. 110, No. 10, pp. 3804-3813. Prepublished online as a Blood First Edition Paper on August 10, 2007; DOI 10.1182/blood-2007-05-091074. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2007-05-091074v1 110/10/3804    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 Chen, X. Articles by Drobyski, W. R. Search for Related Content PubMed PubMed Citation Articles by Chen, X. Articles by Drobyski, W. R. Related Collections Immunobiology Transplantation Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION Absence of regulatory T-cell control of TH1 and TH17 cells is responsible for the autoimmune-mediated pathology in chronic graft-versus-host disease Xiao Chen1,2, Sanja Vodanovic-Jankovic1,2, Bryon Johnson3, Melissa Keller3, Richard Komorowski4, and William R. Drobyski1,2 1 Bone Marrow Transplant Program and the Departments of 2 Medicine 3 Pediatrics, and 4 Pathology, Medical College of Wisconsin, Milwaukee Graft-versus-host disease (GVHD) remains the major complication after allogeneic bone marrow transplantation (BMT). The process whereby acute GVHD mediated by alloreactive donor T cells transitions into chronic GVHD, which is characterized by prominent features of auto-immunity, has long been unresolved. In this study, we demonstrate that GVHD-associated autoimmunity and, by extension, chronic GVHD is attributable to the progressive loss of CD4+CD25+Foxp3+ regulatory T cells during the course of acute GVHD. This leads to the expansion of donor-derived CD4+ T cells with TH1 and TH17 cytokine phenotypes that release proinflammatory cytokines and cause autoimmune-mediated pathological damage. These T cells are present early after transplantation, indicating that the pathophysiological events that lead to chronic GVHD are set in motion during the acute phase of GVHD. We conclude that the absence of CD4+CD25+ regulatory T cells coupled with unregulated TH1 and TH17 cells leads to the development of autoimmunity and that donor-derived TH1 and TH17 cells serve as the nexus between acute and chronic GVHD. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Regulatory T cells and the pursuit of self-tolerance Allan D. Hess Blood 2007 110: 3497-3498. [Full Text] [PDF] This article has been cited by other articles: S Mori and P Levin A brief review of potential mechanisms of immune reconstitution inflammatory syndrome in HIV following antiretroviral therapy Int J STD AIDS, July 1, 2009; 20(7): 447 - 452. [Abstract] [Full Text] [PDF] Z. Mikhak, A. Farsidjani, and A. D. Luster Endotoxin Augmented Antigen-Induced Th1 Cell Trafficking Amplifies Airway Neutrophilic Inflammation J. Immunol., June 15, 2009; 182(12): 7946 - 7956. [Abstract] [Full Text] [PDF] M. M. Imanguli, W. D. Swaim, S. C. League, R. E. Gress, S. Z. Pavletic, and F. T. Hakim Increased T-bet+ cytotoxic effectors and type I interferon-mediated processes in chronic graft-versus-host disease of the oral mucosa Blood, April 9, 2009; 113(15): 3620 - 3630. [Abstract] [Full Text] [PDF] R. Das, X. Chen, R. Komorowski, M. J. Hessner, and W. R. 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IL-17 contributes to CD4-mediated graft-versus-host disease Blood, January 22, 2009; 113(4): 945 - 952. [Abstract] [Full Text] [PDF] D. Zhao, C. Zhang, T. Yi, C.-L. Lin, I. Todorov, F. Kandeel, S. Forman, and D. Zeng In vivo-activated CD103+CD4+ regulatory T cells ameliorate ongoing chronic graft-versus-host disease Blood, September 1, 2008; 112(5): 2129 - 2138. [Abstract] [Full Text] [PDF] P. Muranski, A. Boni, P. A. Antony, L. Cassard, K. R. Irvine, A. Kaiser, C. M. Paulos, D. C. Palmer, C. E. Touloukian, K. Ptak, et al. Tumor-specific Th17-polarized cells eradicate large established melanoma Blood, July 15, 2008; 112(2): 362 - 373. [Abstract] [Full Text] [PDF]

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