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 tis sues, including the eye, testis, and a subset of tumors. We tested whe ther expression of Pas ligand on pancreatic islets either following ad enoviral or germline gene transfer could confer immune privilege after transplantation. Islets were infected with an adenoviral vector conta ining the murine Pas ligand cDNA (AdFasL), and were transplanted into allogenic diabetic hosts. Paradoxically, AdFasL-infected islets underw ent accelerated neutrophilic rejection. The rejection was T cell and B cell independent and required Fas protein expression by host cells, b ut not on islets. Similarly, transgenic mice expressing Fas ligand in pancreatic beta cells developed massive neutrophilic infiltrates and d iabetes at a young age. Thus, Fas ligand expression on pancreatic isle ts results in neutrophilic infiltration and islet destruction. These r esults have important implications for the development of Fas ligand-b ased immunotherapies.