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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 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 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 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. Related Collections Transplantation Gene Therapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 November 2002, Vol. 100, No. 9, pp. 3147-3154 GENE THERAPY Transduction of donor hematopoietic stem-progenitor cells with Fas ligand enhanced short-term engraftment in a murine model of allogeneic bone marrow transplantation Katharine A. Whartenby, Erin E. Straley, Heeje Kim, Frederick Racke, Vivek Tanavde, Kevin S. Gorski, Linzhao Cheng, Drew M. Pardoll, and Curt I. Civin From the Departments of Oncology, Pathology, and Pediatrics, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University School of Medicine, Baltimore, MD. Fas-mediated apoptosis is a major physiologic mechanism by which activated T cells are eliminated after antigen-stimulated clonal expansion generates a specific cellular immune response. Because activated T cells are the major effectors of allograft rejection, we hypothesized that genetically modifying allogeneic bone marrow (BM) cells prior to transplantation 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 antigen-negative (lin) mouse BM cells (lin BMs), in an allogeneic BMT model. FasL-modified lin BMs killed Fas-expressing T cells in vitro. Mice that received transplants of allogeneic FasL+ lin BMs had enhanced short-term engraftment, after nonmyeloablative conditioning, as compared to controls. We observed no major hepatic toxicity or hematopoietic or immune impairment in recipient mice at these time points. These results suggest potential therapeutic approaches by manipulating lymphohematopoietic stem-progenitor cells to express FasL or other immune-modulating genes in the context of BMT. © 2002 by The American Society of Hematology.   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] M. Pearl-Yafe, J. Stein, E. S. Yolcu, D. L. Farkas, H. Shirwan, I. Yaniv, and N. Askenasy Fas Transduces Dual Apoptotic and Trophic Signals in Hematopoietic Progenitors Stem Cells, December 1, 2007; 25(12): 3194 - 3203. [Abstract] [Full Text] [PDF] M. Pearl-Yafe, E. S. Yolcu, J. Stein, O. Kaplan, I. Yaniv, H. Shirwan, and N. Askenasy Fas Ligand Enhances Hematopoietic Cell Engraftment Through Abrogation of Alloimmune Responses and Nonimmunogenic Interactions Stem Cells, June 1, 2007; 25(6): 1448 - 1455. [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] O. Bohana-Kashtan and C. I. Civin Fas Ligand as a Tool for Immunosuppression and Generation of Immune Tolerance Stem Cells, November 1, 2004; 22(6): 908 - 924. [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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