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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 (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 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 Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 18, 2007 Accepted August 7, 2007 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 Chen, Sanja Vodanovic-Jankovic, Bryon Johnson, Melissa Keller, Richard Komorowski, and William R Drobyski* Bone Marrow Transplant Program, Medical College of Wisconsin, Milwaukee, WI, United States Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, United States Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, United States Department of Pathology, Medical College of Wisconsin, Milwaukee, WI, United States * Corresponding author; email: wdrobysk{at}mcw.edu. 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 autoimmunity 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 post 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: T L Freitag, S Rietdijk, Y Junker, Y Popov, A K Bhan, C P Kelly, C Terhorst, and D Schuppan Gliadin-primed CD4+CD45RBlowCD25- T cells drive gluten-dependent small intestinal damage after adoptive transfer into lymphopenic mice Gut, December 1, 2009; 58(12): 1597 - 1605. [Abstract] [Full Text] [PDF] D. Fowler T cells helping GVHD: take-away lessons Blood, October 1, 2009; 114(14): 2858 - 2859. [Full Text] [PDF] T. Yi, Y. Chen, L. Wang, G. Du, D. Huang, D. Zhao, H. Johnston, J. Young, I. Todorov, D. T. Umetsu, et al. Reciprocal differentiation and tissue-specific pathogenesis of Th1, Th2, and Th17 cells in graft-versus-host disease Blood, October 1, 2009; 114(14): 3101 - 3112. [Abstract] [Full Text] [PDF] X. 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[Abstract] [Full Text] [PDF] R. Das, X. Chen, R. Komorowski, M. J. Hessner, and W. R. Drobyski Interleukin-23 secretion by donor antigen-presenting cells is critical for organ-specific pathology in graft-versus-host disease Blood, March 5, 2009; 113(10): 2352 - 2362. [Abstract] [Full Text] [PDF] M. J. Carlson, M. L. West, J. M. Coghill, A. Panoskaltsis-Mortari, B. R. Blazar, and J. S. Serody In vitro-differentiated TH17 cells mediate lethal acute graft-versus-host disease with severe cutaneous and pulmonary pathologic manifestations Blood, February 5, 2009; 113(6): 1365 - 1374. [Abstract] [Full Text] [PDF] L. Strauss, C. Bergmann, and T. L. Whiteside Human Circulating CD4+CD25highFoxp3+ Regulatory T Cells Kill Autologous CD8+ but Not CD4+ Responder Cells by Fas-Mediated Apoptosis J. Immunol., February 1, 2009; 182(3): 1469 - 1480. [Abstract] [Full Text] [PDF] L. W. Kappel, G. L. Goldberg, C. G. King, D. Y. Suh, O. M. Smith, C. Ligh, A. M. Holland, J. Grubin, N. M. Mark, C. Liu, et al. 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