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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 (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 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 Search for Related Content PubMed PubMed Citation Articles by Maeda, Y. Articles by Ferrara, J. L Related Collections Related Article in Blood Online Related Letter in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 22, 2004 Accepted December 3, 2004 Critical role of host T cells in experimental acute graft-versus-host disease Yoshinobu Maeda, Pavan Reddy, Kathleen P Lowler, Chen Liu, D K Bishop, and James L Ferrara* Department of Internal Medicine, University of Michigan Cancer Center, Ann Arbor, MI, USA Department of Pathology, University of Florida College of Medicine, Gainesville, FL, USA Department of General Surgery, University of Michigan Cancer Center, Ann Arbor, MI, USA Department of Internal Medicine, University of Michigan Cancer Center, Ann Arbor, MI, USA; Department of Pediatrics, University of Michigan Cancer Center, Ann Arbor, MI, USA * Corresponding author; email: ferrara{at}umich.edu. 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-TCR monoclonal antibody reduced GVHD and T cell deficient (-/-) BMT recipients markedly improved survival compared to normal controls (63% vs. 10%, P< 0.001). T cells were responsible for this difference because reconstitution of -/- recipients with T cells restored GVHD mortality. -/- recipients showed decreased serum levels of 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 co-cultured with Tcells than DCs co-cultured with medium alone. This enhancement did not depend on IFN-, TNF- or CD40 ligand but did depend on cell-cell contact. These data demonstrated that the host T cells exacerbate GVHD by enhancing the allostimulatory capacity of host antigen presenting cells. 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. 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[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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