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Prepublished online as a Blood First Edition Paper on June 21, 2002; DOI 10.1182/blood-2002-01-0118. This Article Full Text (PDF) All Versions of this Article: 2002-01-0118v1 100/9/3147    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 Whartenby, K. A Articles by Civin, C. I Search for Related Content PubMed PubMed Citation Articles by Whartenby, K. A Articles by Civin, C. I Social Bookmarking                   What's this? Submitted January 15, 2002 Accepted June 10, 2002 Transduction of donor hematopoietic stem-progenitor cells with Fas ligand enhanced short-term engraftment in a murine model of allogeneic bone marrow transplant Katharine A Whartenby*, Erin E Straley, HeeJe Kim, Frederick Racke, Vivek Tanavde, Kevin S Gorski, Linzhao Cheng, Drew M Pardoll, and Curt I Civin Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA * Corresponding author; email: whartka{at}jhmi.edu. Fas-mediated apoptosis is a major physiologic mechanism by which activated T cells are eliminated after antigen (Ag)-stimulated clonal expansion generates a specific cellular immune response. Since activated T cells are the major effectors of allograft rejection, we hypothesized that genetically modifying allogeneic bone marrow (BM) cells prior to transplant could provide some protection from host T cell attack, thus enhancing donor cell engraftment in bone marrow transplantation (BMT). We undertook studies to determine the outcome of lentiviral vector-mediated transduction of Fas ligand (FasL) into lineage Ag-negative (lin-) mouse BM cells (lin- BMs), in an allogeneic BMT model. FasL modified lin- BMs killed Fas-expressing T cells in vitro. Mice transplanted with allogeneic FasL+ lin- BMs had enhanced short-term engraftment, after non-myeloablative conditioning, as compared to controls. We observed no major hepatic toxicity, or hematopoietic or immune impairment, of recipient mice at these time points. These results suggest potential therapeutic approaches by manipulating lympho-hematopoietic stem-progenitor cells to express FasL or other immune modulating genes in the context of BMT. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: E. S. Yolcu, X. Gu, C. Lacelle, H. Zhao, L. Bandura-Morgan, N. Askenasy, and H. Shirwan Induction of Tolerance to Cardiac Allografts Using Donor Splenocytes Engineered to Display on Their Surface an Exogenous Fas Ligand Protein J. Immunol., July 15, 2008; 181(2): 931 - 939. [Abstract] [Full Text] [PDF] C. Schutz, M. Fleck, A. Mackensen, A. Zoso, D. Halbritter, J. P. Schneck, and M. Oelke Killer artificial antigen-presenting cells: a novel strategy to delete specific T cells Blood, April 1, 2008; 111(7): 3546 - 3552. [Abstract] [Full Text] [PDF] N. Askenasy, E. S. Yolcu, I. Yaniv, and H. Shirwan Induction of tolerance using Fas ligand: a double-edged immunomodulator Blood, February 15, 2005; 105(4): 1396 - 1404. [Abstract] [Full Text] [PDF] R. Greil, G. Anether, K. Johrer, and I. Tinhofer Tracking death dealing by Fas and TRAIL in lymphatic neoplastic disorders: pathways, targets, and therapeutic tools J. Leukoc. Biol., September 1, 2003; 74(3): 311 - 330. [Abstract] [Full Text] [PDF] S. Hoves, S. W. Krause, D. Halbritter, H.-G. Zhang, J. D. Mountz, J. Scholmerich, and M. Fleck Mature But Not Immature Fas Ligand (CD95L)-Transduced Human Monocyte-Derived Dendritic Cells Are Protected from Fas-Mediated Apoptosis and Can Be Used as Killer APC J. Immunol., June 1, 2003; 170(11): 5406 - 5413. [Abstract] [Full Text] [PDF]

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