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Blood, 1 October 2009, Vol. 114, No. 14, pp. 3101-3112. Prepublished online as a Blood First Edition Paper on July 14, 2009; DOI 10.1182/blood-2009-05-219402. This Article Full Text Full Text (PDF) Supplemental Methods and Figures All Versions of this Article: blood-2009-05-219402v1 114/14/3101    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 Google Scholar Articles by Yi, T. Articles by Zeng, D. PubMed PubMed Citation Articles by Yi, T. Articles by Zeng, D. Related Collections Transplantation Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION Reciprocal differentiation and tissue-specific pathogenesis of Th1, Th2, and Th17 cells in graft-versus-host disease Tangsheng Yi1,2, Ying Chen1, Lin Wang1,2, Gong Du1, Daniel Huang2, Dongchang Zhao1, Heather Johnston1,2, James Young1,2, Ivan Todorov1, Dale T. Umetsu3, Lieping Chen4, Yoichiro Iwakura5, Fouad Kandeel1, Stephen Forman1, and Defu Zeng1,2 1 The Beckman Research Institute, City of Hope, Duarte, CA; 2 Irell & Manella Graduate School of Biological Sciences, City of Hope, Duarte, CA; 3 Children's Hospital, Harvard Medical School, Boston, MA; 4 Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD; and 5 Institute of Medical Science, University of Tokyo, Tokyo, Japan In acute graft-versus-host disease (GVHD), naive donor CD4+ T cells recognize alloantigens on host antigen-presenting cells and differentiate into T helper (Th) subsets (Th1, Th2, and Th17 cells), but the role of Th subsets in GVHD pathogenesis is incompletely characterized. Here we report that, in an MHC-mismatched model of C57BL/6 donor to BALB/c recipient, WT donor CD4+ T cells predominantly differentiated into Th1 cells and preferentially mediated GVHD tissue damage in gut and liver. However, absence of interferon- (IFN-) in CD4+ T cells resulted in augmented Th2 and Th17 differentiation and exacerbated tissue damage in lung and skin; absence of both IL-4 and IFN- resulted in augmented Th17 differentiation and preferential, although not exclusive, tissue damage in skin; and absence of both IFN- and IL-17 led to further augmentation of Th2 differentiation and idiopathic pneumonia. The tissue-specific GVHD mediated by Th1, Th2, and Th17 cells was in part associated with their tissue-specific migration mediated by differential expression of chemokine receptors. Furthermore, lack of tissue expression of the IFN-–inducible B7-H1 played a critical role in augmenting the Th2-mediated idiopathic pneumonia. These results indicate donor CD4+ T cells can reciprocally differentiate into Th1, Th2, and Th17 cells that mediate organ-specific GVHD. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: T cells helping GVHD: take-away lessons Daniel Fowler Blood 2009 114: 2858-2859. [Full Text] [PDF] This article has been cited by other articles: D. Fowler T cells helping GVHD: take-away lessons Blood, October 1, 2009; 114(14): 2858 - 2859. [Full Text] [PDF]

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