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Blood, 15 October 2008, Vol. 112, No. 8, pp. 3508-3516. Prepublished online as a Blood First Edition Paper on July 9, 2008; DOI 10.1182/blood-2007-09-113670. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-09-113670v1 112/8/3508    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 Taylor, P. A. Articles by Blazar, B. R. Search for Related Content PubMed PubMed Citation Articles by Taylor, P. A. Articles by Blazar, B. R. Related Collections Transplantation Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION TLR agonists regulate alloresponses and uncover a critical role for donor APCs in allogeneic bone marrow rejection Patricia A. Taylor1, Michael J. Ehrhardt1, Christopher J. Lees1, Angela Panoskaltsis-Mortari1, Arthur M. Krieg2, Arlene H. Sharpe3, William J. Murphy4, Jonathan S. Serody5, Hiroaki Hemmi6, Shizuo Akira6, Robert B. Levy7, and Bruce R. Blazar1 1 Cancer Center and the Department of Pediatrics, Division of BMT, University of Minnesota, Minneapolis; 2 Pfizer, Cambridge, MA; 3 Harvard Medical School and Brigham and Women's Hospital, Boston, MA; 4 Department of Microbiology and Immunology, University of Nevada School of Medicine, Reno; 5 Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill; 6 Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan; and 7 Department of Microbiology and Immunology, University of Miami, FL Cytosine-phosphorothioate-guanine oligodeoxynucleotides (CpG ODNs) are synthetic ODNs with unmethylated DNA sequences that mimic viral and bacterial DNA and protect against infectious agents and tumor challenge. We show that CpG ODNs markedly accelerated graft-versus-host disease (GVHD) lethality by Toll-like receptor 9 (TLR9) ligation of host antigen-presenting cells (APCs), dependent upon host IFN but independent of host IL-12, IL-6, or natural killer (NK) cells. Imaging studies showed significantly more green fluorescent protein–positive (GFP+) effector T cells in lymphoid and nonlymphoid organs. In engraftment studies, CpG ODNs promoted allogeneic donor bone marrow (BM) rejection independent of host IFN, IL-12, or IL-6. During the course of these studies, we uncovered a previously unknown and critical role of donor BM APCs in modulating the rejection response. CpG ODNs promoted BM rejection by ligation of donor BM, but not host, TLR9. CpG ODNs did not impair engraftment of TLR9–/– BM unless wild-type myeloid (CD11b+) but not B-lineage (CD19+) BM cells were added to the donor inoculum. The importance of donor BM APCs in modulating the strength of the host antidonor rejection response was underscored by the finding that B7-1/B7-2–/– BM was less likely than wild-type BM to be rejected. Collectively, these data offer new insight into the mechanism of alloresponses regulating GVHD and BM rejection. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Donor dendritic cells dance the do-si-do in allogeneic transplantation Edmund K. Waller and Jian-Ming Li Blood 2008 112: 3007-3008. [Full Text] [PDF] This article has been cited by other articles: L. Chen, E. Ahmed, T. Wang, Y. Wang, J. Ochando, A. S. Chong, and M.-L. Alegre TLR Signals Promote IL-6/IL-17-Dependent Transplant Rejection J. Immunol., May 15, 2009; 182(10): 6217 - 6225. [Abstract] [Full Text] [PDF] J. Wilson, H. Cullup, R. Lourie, Y. Sheng, A. Palkova, K. J. Radford, A. M. Dickinson, A. M. Rice, D. N.J. Hart, and D. J. Munster Antibody to the dendritic cell surface activation antigen CD83 prevents acute graft-versus-host disease J. Exp. Med., February 16, 2009; 206(2): 387 - 398. [Abstract] [Full Text] [PDF]

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