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Blood, 15 February 2007, Vol. 109, No. 4, pp. 1756-1764. Prepublished online as a Blood First Edition Paper on October 10, 2006; DOI 10.1182/blood-2006-08-042853. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-08-042853v1 109/4/1756    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 Sakoda, Y. Articles by Teshima, T. Search for Related Content PubMed PubMed Citation Articles by Sakoda, Y. Articles by Teshima, T. Related Collections Transplantation Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION Donor-derived thymic-dependent T cells cause chronic graft-versus-host disease Yukimi Sakoda1,2, Daigo Hashimoto3, Shoji Asakura2, Kengo Takeuchi4, Mine Harada1, Mitsune Tanimoto2, and Takanori Teshima3 1 Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Science, Fukuoka, Japan; 2 Biopathological Science, Okayama University Graduate School of Medicine and Dentistry, Japan; 3 Center for Cellular and Molecular Medicine, Kyushu University Hospital, Fukuoka, Japan; 4 Pathology, Japanese Foundation for Cancer Institute, Tokyo, Japan Chronic graft-versus-host disease (GVHD) is the most common cause of poor long-term outcomes after allogeneic bone marrow transplantation (BMT), but the pathophysiology of chronic GVHD still remains poorly understood. We tested the hypothesis that the impaired thymic negative selection of the recipients will permit the emergence of pathogenic T cells that cause chronic GVHD. Lethally irradiated C3H/HeN (H-2k) recipients were reconstituted with T-cell–depleted bone marrow cells from major histocompatibility complex [MHC] class II–deficient (H2-Ab1–/–) B6 (H-2b) mice. These mice developed diseases that showed all of the clinical and histopathological features of human chronic GVHD. Thymectomy prevented chronic GVHD, thus confirming the causal association of the thymus. CD4+ T cells isolated from chronic GVHD mice were primarily donor reactive, and adoptive transfer of CD4+ T cells generated in these mice caused chronic GVHD in C3H/HeN mice in the presence of B6-derived antigen-presenting cells. Our results demonstrate for the first time that T cells that escape from negative thymic selection could cause chronic GVHD after allogeneic BMT. These results also suggest that self-reactivity of donor T cells plays a role in this chronic GVHD, and improvement in the thymic function may have a potential to decrease chronic GVHD. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. Chakraverty and M. Sykes The role of antigen-presenting cells in triggering graft-versus-host disease and graft-versus-leukemia Blood, July 1, 2007; 110(1): 9 - 17. [Abstract] [Full Text] [PDF]

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