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Blood, 1 October 2006, Vol. 108, No. 7, pp. 2463-2469. Prepublished online as a Blood First Edition Paper on June 6, 2006; DOI 10.1182/blood-2006-04-019059. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2006-04-019059v1 108/7/2463    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 Blaser, B. W. Articles by Caligiuri, M. A. Search for Related Content PubMed PubMed Citation Articles by Blaser, B. W. Articles by Caligiuri, M. A. Related Collections Hemostasis, Thrombosis, and Vascular Biology Immunobiology Neoplasia Free Research Articles Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION Trans-presentation of donor-derived interleukin 15 is necessary for the rapid onset of acute graft-versus-host disease but not for graft-versus-tumor activity Bradley W. Blaser, Noah R. Schwind, Seth Karol, Dennis Chang, Samuel Shin, Sameek Roychowdhury, Brian Becknell, Amy K. Ferketich, Donna F. Kusewitt, Bruce R. Blazar, and Michael A. Caligiuri From the Integrated Biomedical Sciences Graduate Program; the Department of Internal Medicine, Division of Hematology/Oncology; the Department of Molecular Virology, Immunology, and Medical Genetics; the Division of Epidemiology; the Department of Veterinary Biosciences; the Comprehensive Cancer Center at The Ohio State University, Columbus; the Cancer Center and the Department of Pediatrics, Division of Hematology, Oncology and Bone Marrow Transplantation, University of Minnesota Cancer Center, Minneapolis. The "holy grail" of allogeneic stem cell transplantation is to preserve the graft-versus-tumor (GVT) effect while eliminating graft-versus-host disease (GVHD). Endogenous donor-derived interleukin 15 (IL-15) has been implicated in the pathogenesis of acute GVHD, yet the mechanism by which it impacts this lethal process remains unclear. Using the well-described and clinically relevant C57BL/6 B6D2F1 murine model of acute GVHD, we demonstrate that in trans presentation of IL-15 by donor bone marrow–derived cells is required for the rapid onset of acute GVHD. Recipients of IL-15–/– C57BL/6 bone marrow cells show diminished type 1 polarization of T cells, yet there is no decrease in donor T-cell reconstitution. A molecular basis for these findings is provided with the observation that expression of T-bet, the master control gene for type 1 T-cell functions, is necessary for IL-15–mediated acute GVHD lethality. Finally, we demonstrate that in the absence of donor-derived IL-15, the GVT effect is maintained. These findings thus establish a mechanism by which endogenous donor-derived IL-15 impacts the pathobiology of acute GVHD and GVT activity. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Trans-presentation of IL-15 Jerome Ritz Blood 2006 108: 2135-2136. [Full Text] [PDF] This article has been cited by other articles: 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]

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