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Blood, 5 February 2009, Vol. 113, No. 6, pp. 1365-1374. Prepublished online as a Blood First Edition Paper on October 28, 2008; DOI 10.1182/blood-2008-06-162420. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-06-162420v1 113/6/1365    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 Carlson, M. J Articles by Serody, J. S Search for Related Content PubMed PubMed Citation Articles by Carlson, M. J Articles by Serody, J. S Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 12, 2008 Accepted October 21, 2008 In vitro differentiated TH17 cells mediate lethal acute graft-versus-host disease with severe cutaneous and pulmonary pathology Michael J Carlson, Michelle L West, James M Coghill, Angela Panoskaltsis-Mortari, Bruce R Blazar, and Jonathan S Serody* Departments of Medicine, Microbiology, and Immunology and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, United States Department of Pediatrics, Division of Blood and Marrow Transplantation, University of Minnesota Cancer Center, Minneapolis, MN, United States * Corresponding author; email: jonathan_serody{at}med.unc.edu. The morbidity and mortality associated with graft-host-disease (GVHD) is a significant obstacle to the greater use of allogeneic stem cell transplantation. Donor T cells that predominantly differentiate into TH1/Tc1 T cells and generate pro-inflammatory cytokines such as IFN- mediate GVHD. Although numerous studies have described a pathogenic role for IFN-, multiple reports have demonstrated that the lack of IFN- paradoxically exacerbated GVHD lethality. This has led to speculation that another subset of T cells may significantly contribute to GVHD mortality. Recently, several groups have demonstrated a new lineage of CD4+ T helper cell development distinct from TH1 or TH2 differentiation. This lineage is characterized by production of IL-17A, IL-17F, IL-22, and IL-21 and have been termed TH17 cells. Here, we demonstrate that a highly purified population of TH17 cells is capable of inducing lethal GVHD, hallmarked by extensive cutaneous and pulmonary pathology. Upon transfer these cells migrate to and expand in GVHD target organs and secondary lymphoid tissues. Lastly, we demonstrate differential roles for TNF- and IL-17A in the clinical manifestations of GVHD induced by TH17 cells. Our studies demonstrate that cells other than TH1/Tc1 can mediate acute GVHD. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. Socie and B. R. Blazar Acute graft-versus-host disease: from the bench to the bedside Blood, November 12, 2009; 114(20): 4327 - 4336. [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. Chen, R. Das, R. Komorowski, A. Beres, M. J. Hessner, M. Mihara, and W. R. Drobyski Blockade of interleukin-6 signaling augments regulatory T-cell reconstitution and attenuates the severity of graft-versus-host disease Blood, July 23, 2009; 114(4): 891 - 900. [Abstract] [Full Text] [PDF]

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