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Blood, 15 January 2005, Vol. 105, No. 2, pp. 894-901. Prepublished online as a Blood First Edition Paper on September 16, 2004; DOI 10.1182/blood-2004-05-1687. This Article Full Text (PDF) All Versions of this Article: 2004-05-1687v1 105/2/894    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 Blaser, B. W Articles by Guimond, M. Search for Related Content PubMed PubMed Citation Articles by Blaser, B. W Articles by Guimond, M. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 3, 2004 Accepted September 3, 2004 Donor Derived IL-15 is Critical for Acute Allogeneic Graft-Versus-Host Disease Bradley W Blaser, Sameek Roychowdhury, Daniel J Kim, Noah R Schwind, Darshna Bhatt, Weifeng Yuan, Donna F Kusewitt, Amy K Ferketich, Michael A Caligiuri*, and Martin Guimond The Integrated Biomedical Sciences Graduate Program, The Ohio State University, Columbus, OH, USA Division of Human Cancer Genetics, Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, OH, USA Department of Veterinary Biosciences, The Ohio State University, Columbus, OH, USA; The Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA Division of Epidemiology and Biometrics, The Ohio State University, Columbus, OH, USA; The Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA The Integrated Biomedical Sciences Graduate Program, The Ohio State University, Columbus, OH, USA; Division of Human Cancer Genetics, Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, OH, USA; Department of Veterinary Biosciences, The Ohio State University, Columbus, OH, USA * Corresponding author; email: caligiuri-1{at}medctr.osu.edu. Interleukin (IL)-15 is a pleiotropic pro-inflammatory cytokine with inefficient post-transcriptional processing. We hypothesized that endogenous IL-15 could affect disease progression in the well-described C57Bl/6 (B6)(C57Bl/6 x DBA/2) F1 hybrid (B6D2F1) murine model of acute allogeneic graft-versus-host disease (GVHD). B6D2F1 allogeneic recipients were transplanted with IL-15-/- B6 bone marrow cells or B6 bone marrow cells expressing a murine IL-15 transgene (IL-15 tg) modified for efficient translation and secretion. Mice transplanted with IL-15-/- B6 bone marrow cells displayed a significantly longer median survival time (MST) compared to mice transplanted with wild type (wt) B6 bone marrow; in contrast, mice transplanted with IL-15 tg B6 bone marrow cells had a dramatically decreased MST. This decrease in survival was associated with a substantial activation and expansion of effector-memory (CD44highCD62Llow) CD8+ T lymphocytes. Finally, in vivo depletion of either CD4+ or CD8+ T lymphocyte subsets significantly prolonged survival in mice receiving IL-15 tg B6 marrow, while depletion of both CD4+ and CD8+ T cells provided complete protection from acute GVHD. We thus show that acute GVHD is attenuated in the absence of donor bone marrow-derived IL-15 and conclude that donor-derived IL-15 is a critical mediator of T cell function in acute GVHD. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. B. Sunwoo, S. Kim, L. Yang, T. Naik, D. A. Higuchi, J. L. Rubenstein, and W. M. Yokoyama Distal-less homeobox transcription factors regulate development and maturation of natural killer cells PNAS, August 5, 2008; 105(31): 10877 - 10882. [Abstract] [Full Text] [PDF] N. Dulphy, P. Haas, M. Busson, S. Belhadj, R. Peffault de Latour, M. Robin, M. Carmagnat, P. Loiseau, R. Tamouza, C. Scieux, et al. An Unusual CD56brightCD16low NK Cell Subset Dominates the Early Posttransplant Period following HLA-Matched Hematopoietic Stem Cell Transplantation J. Immunol., August 1, 2008; 181(3): 2227 - 2237. [Abstract] [Full Text] [PDF] G. Cassese, E. Parretta, L. Pisapia, A. Santoni, J. Guardiola, and F. Di Rosa Bone marrow CD8 cells down-modulate membrane IL-7R{alpha} expression and exhibit increased STAT-5 and p38 MAPK phosphorylation in the organ environment. Blood, September 15, 2007; 110(6): 1960 - 1969. [Abstract] [Full Text] [PDF] B. W. Blaser, N. R. Schwind, S. Karol, D. Chang, S. Shin, S. Roychowdhury, B. Becknell, A. K. Ferketich, D. F. Kusewitt, B. R. Blazar, et al. 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 Blood, October 1, 2006; 108(7): 2463 - 2469. [Abstract] [Full Text] [PDF] J. E. Foley, U. Jung, A. Miera, T. Borenstein, J. Mariotti, M. Eckhaus, B. E. Bierer, and D. H. Fowler Ex Vivo Rapamycin Generates Donor Th2 Cells That Potently Inhibit Graft-versus-Host Disease and Graft-versus-Tumor Effects via an IL-4-Dependent Mechanism J. Immunol., November 1, 2005; 175(9): 5732 - 5743. [Abstract] [Full Text] [PDF] S. Roychowdhury, B. W. Blaser, A. G. Freud, K. Katz, D. Bhatt, A. K. Ferketich, V. Bergdall, D. Kusewitt, R. A. Baiocchi, and M. A. Caligiuri IL-15 but not IL-2 rapidly induces lethal xenogeneic graft-versus-host disease Blood, October 1, 2005; 106(7): 2433 - 2435. [Abstract] [Full Text] [PDF]

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