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Blood, 15 July 2005, Vol. 106, No. 2, pp. 749-755. Prepublished online as a Blood First Edition Paper on March 29, 2005; DOI 10.1182/blood-2004-10-4087. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-10-4087v1 106/2/749    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 Maeda, Y. Articles by Ferrara, J. L. M. Search for Related Content PubMed PubMed Citation Articles by Maeda, Y. Articles by Ferrara, J. L. M. Related Collections Immunobiology Transplantation Related Article in Blood Online Related Letter in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION Critical role of host T cells in experimental acute graft-versus-host disease Yoshinobu Maeda, Pavan Reddy, Kathleen P. Lowler, Chen Liu, Dennis Keith Bishop, and James L. M. Ferrara From the Departments of Internal Medicine, General Surgery, and Pediatrics, University of Michigan Cancer Center, Ann Arbor, MI; and the Department of Pathology, University of Florida College of Medicine, Gainesville. T cells localize to target tissues of graft-versus-host disease (GVHD) and therefore we investigated the role of host T cells in the pathogenesis of acute GVHD in several well-characterized allogeneic bone marrow transplantation (BMT) models. Depletion of host T cells in wild-type (wt) B6 recipients by administration of anti-T-cell receptor (TCR) monoclonal antibody reduced GVHD, and T-cell-deficient (-/-) BM transplant recipients experienced markedly improved survival compared with normal controls (63% vs 10%, P < .001). T cells were responsible for this difference because reconstitution of -/- recipients with T cells restored GVHD mortality. -/- recipients showed decreased serum levels of tumor necrosis factor (TNF-), less GVHD histopathologic damage, and reduced donor T-cell expansion. Mechanistic analysis of this phenomenon demonstrated that dendritic cells (DCs) from -/- recipients exhibited less allostimulatory capacity compared to wt DCs after irradiation. Normal DCs derived from BM caused greater allogeneic T-cell proliferation when cocultured with T cells than DCs cocultured with medium alone. This enhancement did not depend on interferon (IFN-), TNF-, or CD40 ligand but did depend on cell-to-cell contact. These data demonstrated that the host T cells exacerbate GVHD by enhancing the allostimulatory capacity of host antigen-presenting cells. (Blood. 2005;106:749-755) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Host T cells: an innate bridge to the epithelial targets of GVHD? Geoffrey R. Hill Blood 2005 106: 393-394. [Full Text] [PDF] Related Letter in Blood Online: Recipient T cells in graft-versus-host disease Britt E. Anderson, Warren D. Shlomchik, Mark J. Shlomchik, James L. M. Ferrara, and Pavan Reddy Blood 2006 107: 3808-3809. [Full Text] [PDF] This article has been cited by other articles: M. A. Flierl, D. Rittirsch, H. Gao, L. M. Hoesel, B. A. Nadeau, D. E. Day, F. S. Zetoune, J. V. Sarma, M. S. Huber-Lang, J. L. M. Ferrara, et al. Adverse functions of IL-17A in experimental sepsis FASEB J, July 1, 2008; 22(7): 2198 - 2205. [Abstract] [Full Text] [PDF] K. Hochegger, T. Schatz, P. Eller, A. Tagwerker, D. Heininger, G. Mayer, and A. R. Rosenkranz Role of {alpha}/beta and {gamma}/{delta} T cells in renal ischemia-reperfusion injury Am J Physiol Renal Physiol, September 1, 2007; 293(3): F741 - F747. [Abstract] [Full Text] [PDF] 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] C. Pabst, H. Schirutschke, G. Ehninger, M. Bornhauser, and U. Platzbecker The Graft Content of Donor T Cells Expressing {gamma}{delta}TCR+ and CD4+foxp3+ Predicts the Risk of Acute Graft versus Host Disease after Transplantation of Allogeneic Peripheral Blood Stem Cells from Unrelated Donors Clin. Cancer Res., May 15, 2007; 13(10): 2916 - 2922. [Abstract] [Full Text] [PDF] V. Rowe, T. Banovic, K. P. MacDonald, R. Kuns, A. L. Don, E. S. Morris, A. C. Burman, H. M. Bofinger, A. D. Clouston, and G. R. Hill Host B cells produce IL-10 following TBI and attenuate acute GVHD after allogeneic bone marrow transplantation Blood, October 1, 2006; 108(7): 2485 - 2492. [Abstract] [Full Text] [PDF] B. E. Anderson, W. D. Shlomchik, M. J. Shlomchik, J. L. M. Ferrara, and P. Reddy Recipient {gamma}{delta} T cells in graft-versus-host disease. Blood, May 1, 2006; 107(9): 3808 - 3809. [Full Text] [PDF]

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