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Fas ligand expression in islets of Langerhans does not confer immune privilege and instead targets them for rapid destruction

Nature Medicine volume 3, pages 738–743 (1997)Cite this article

Abstract

Fas ligand is believed to mediate immune privilege in a variety of tissues, including the eye, testis, and a subset of tumors. We tested whether expression of Fas ligand on pancreatic islets either following adenovirai or germline gene transfer could confer immune privilege after transplantation. Islets were infected with an adenovirai vector containing the murine Fas ligand cDNA (AdFasL), and were transplanted into allogenic diabetic hosts. Paradoxically, AdFasL-infected islets underwent accelerated neutrophilic rejection. The rejection was T cell and B cell independent and required Fas protein expression by host cells, but not on islets. Similarly, transgenic mice expressing Fas ligand in pancreatic β cells developed massive neutrophilic infiltrates and diabetes at a young age. Thus, Fas ligand expression on pancreatic islets results in neutrophilic infiltration and islet destruction. These results have important implications for the development of Fas ligand-based immunotherapies.

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Authors and Affiliations

  1. Department of Medicine, Department of Microbiology and Immunology,

    Sang-Mo Kang & Steinunn Baekkeskov

  2. Hormone Research Institute, University of California at San Francisco, Box 0534, 513 Parnassus Avenue, San Francisco, California, 94143, USA

    Sang-Mo Kang & Steinunn Baekkeskov

  3. Transplantation Research Laboratory, Department of Surgery, University of California at San Francisco, Box 0116, 513 Parnassus Avenue, San Francisco, California, 94143, USA

    Sang-Mo Kang, Zhonghua Lin & Peter G. Stock

  4. Department of Medicine and Gladstone Institute of Cardiovascular Disease, University of California at San Francisco, PO Box 419100, San Francisco, California, 94141-9100, USA

    Darren B. Schneider & David A. Dichek

  5. Department of Biochemistry and Biophysics, and Hormone Research Institute, University of California at San Francisco, Box 0534, 513 Parnassus Avenue, San Francisco, California, 94143, USA

    Douglas Hanahan

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Kang, SM., Schneider, D., Lin, Z. et al. Fas ligand expression in islets of Langerhans does not confer immune privilege and instead targets them for rapid destruction. Nat Med 3, 738–743 (1997). https://doi.org/10.1038/nm0797-738

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