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Blood, 1 March 2005, Vol. 105, No. 5, pp. 2227-2234. Prepublished online as a Blood First Edition Paper on November 2, 2004; DOI 10.1182/blood-2004-08-3032. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-08-3032v1 105/5/2227    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 Anderson, B. E. Articles by Shlomchik, M. J. Search for Related Content PubMed PubMed Citation Articles by Anderson, B. E. Articles by Shlomchik, M. J. Related Collections Immunobiology Transplantation Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION Distinct roles for donor- and host-derived antigen-presenting cells and costimulatory molecules in murine chronic graft-versus-host disease: requirements depend on target organ Britt E. Anderson, Jennifer M. McNiff, Dhanpat Jain, Bruce R. Blazar, Warren D. Shlomchik, and Mark J. Shlomchik From the Section of Immunobiology; the Department of Dermatology; the Department of Pathology; the Department of Laboratory Medicine; and the Section of Oncology, Yale University School of Medicine, New Haven, CT; and the Cancer Center and Department of Pediatrics, Division of Bone Marrow Transplantation, University of Minnesota, Minneapolis. The application of allogeneic stem cell transplantation (alloSCT) is limited by graft-versus-host disease (GVHD). GVHD can be divided into acute and chronic forms that likely have different requirements for initiation and pathogenesis mechanisms. In prior studies we demonstrated that residual host antigen-presenting cells (APCs) were required to initiate acute GVHD (aGVHD) mediated by CD8 T cells. In contrast, here we demonstrate that either donor or host APCs can initiate CD4-mediated GVHD in a model that has features of chronic GVHD (cGVHD). Both donor and host APCs must provide CD80/86-dependent costimulation to elicit maximal cGVHD, and there is no GVHD when both donor and host lack CD80/86. Finally, we were surprised to find that, although either donor or host APCs are sufficient to stimulate skin cGVHD, donor APCs play a dominant role in intestinal cGVHD. Both CD40 and CD80/86 are critical for donor APC function in intestinal cGVHD, but only CD80/86 is required for skin cGVHD. Thus, there are target-tissue–specific differences in APC requirements. These results identify differences in APC requirements between CD8-mediated aGVHD and CD4-mediated cGVHD. They further highlight donor APCs as additional targets for GVHD therapy. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. A. Markey, T. Banovic, R. D. Kuns, S. D. Olver, A. L. J. Don, N. C. Raffelt, Y. A. Wilson, L. J. Raggatt, A. R. Pettit, J. S. Bromberg, et al. Conventional dendritic cells are the critical donor APC presenting alloantigen after experimental bone marrow transplantation Blood, May 28, 2009; 113(22): 5644 - 5649. [Abstract] [Full Text] [PDF] K. Sato, K. Eizumi, T. Fukaya, S. Fujita, Y. Sato, H. Takagi, M. Yamamoto, N. Yamashita, A. Hijikata, H. Kitamura, et al. Naturally occurring regulatory dendritic cells regulate murine cutaneous chronic graft-versus-host disease Blood, May 7, 2009; 113(19): 4780 - 4789. [Abstract] [Full Text] [PDF] M. Christopeit, V. Schutte, S. Theurich, T. 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