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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 (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 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 Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 6, 2004 Accepted October 28, 2004 Distinct roles for donor-and host-derived antigen presenting cells and costimulatory molecules in murine chronic graft vs. 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* Section of Immunobiology, Yale University School of Medicine, New Haven, CT, USA Department of Dermatology, Yale University School of Medicine, New Haven, CT, USA; Department of Pathology, Yale University School of Medicine, New Haven, CT, USA Department of Pathology, Yale University School of Medicine, New Haven, CT, USA Cancer Center and Department of Pediatrics, Division of Bone Marrow Transplantation, University of Minnesota, Minneapolis, MN, USA Section of Immunobiology, Yale University School of Medicine, New Haven, CT, USA; Section of Oncology, Yale University School of Medicine, New Haven, CT, USA Section of Immunobiology, Yale University School of Medicine, New Haven, CT, USA; Laboratory Medicine, Yale University School of Medicine, New Haven, CT, USA * Corresponding author; email: mark.shlomchik{at}yale.edu. The application of allogeneic stem cell transplantation (alloSCT) is limited by graft-vs.-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 while 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. 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