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Blood, 15 February 2005, Vol. 105, No. 4, pp. 1396-1404. Prepublished online as a Blood First Edition Paper on October 14, 2004; DOI 10.1182/blood-2004-06-2364. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-06-2364v1 105/4/1396    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 Askenasy, N. Articles by Shirwan, H. Search for Related Content PubMed PubMed Citation Articles by Askenasy, N. Articles by Shirwan, H. Related Collections Hemostasis, Thrombosis, and Vascular Biology Immunobiology Transplantation Apoptosis Reviews in Translational Hematology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  REVIEWS IN TRANSLATIONAL HEMATOLOGY Induction of tolerance using Fas ligand: a double-edged immunomodulator Nadir Askenasy, Esma S. Yolcu, Isaac Yaniv, and Haval Shirwan From the Frankel Laboratory, Center for Stem Cell Research, Department of Pediatric Hematology-Oncology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel; and the Institute for Cellular Therapeutics and Department of Microbiology and Immunology, University of Louisville, Louisville, KY. Abstract Apoptosis mediated by Fas ligand (FasL) interaction with Fas receptor plays a pivotal regulatory role in immune homeostasis, immune privilege, and self-tolerance. FasL, therefore, has been extensively exploited as an immunomodulatory agent to induce tolerance to both autoimmune and foreign antigens with conflicting results. Difficulties associated with the use of FasL as a tolerogenic factor may arise from (1) its complex posttranslational regulation, (2) the opposing functions of different forms of FasL, (3) different modes of expression, systemic versus localized and transient versus continuous, (4) the level and duration of expression, (5) the sensitivity of target tissues to Fas/FasL-mediated apoptosis and the efficiency of antigen presentation in these tissues, and (6) the types and levels of cytokines, chemokines, and metalloproteinases in the extracellular milieu of the target tissues. Thus, the effective use of FasL as an immunomodulator to achieve durable antigen-specific immune tolerance requires careful consideration of all of these parameters and the design of treatment regimens that maximize tolerogenic efficacy, while minimizing the non-tolerogenic and toxic functions of this molecule. This review summarizes the current status of FasL as a tolerogenic agent, problems associated with its use as an immunomodulator, and new strategies to improve its therapeutic potential. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. Strauss, J. A. Lindquist, N. Arhel, E. Felder, S. Karl, T. L. Haas, S. Fulda, H. Walczak, F. Kirchhoff, and K.-M. Debatin CD95 co-stimulation blocks activation of naive T cells by inhibiting T cell receptor signaling J. Exp. Med., June 8, 2009; 206(6): 1379 - 1393. [Abstract] [Full Text] [PDF] S. Buonocore, N. O. Haddou, F. Moore, S. Florquin, F. Paulart, C. 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