Fas ligand expression in islets of Langerhans does not confer immune privilege and instead targets them for rapid destruction.
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 adenoviral or germline gene transfer could confer immune privilege after transplantation. Islets were infected with an adenoviral 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 beta 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.
Kang
S M
SM
Department of Medicine, Hormone Research Institute, University of California at San Francisco 94143, USA.
Schneider
D B
DB
Lin
Z
Z
Hanahan
D
D
Dichek
D A
DA
Stock
P G
PG
Baekkeskov
S
S
D000256:Adenoviridae; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D017690:Cell Transplantation; D003921:Diabetes Mellitus, Experimental; D053222:Fas Ligand Protein; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006084:Graft Rejection / Q000276:immunology*; D007515:Islets of Langerhans / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D009504:Neutrophils / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014170:Transformation, Genetic; D014181:Transplantation Immunology; D019014:fas Receptor / Q000276:immunology
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D019014:fas Receptor