Expression of human Fas ligand on mouse beta islet cells does not induce insulitis but is insufficient to confer immune privilege for islet grafts

Fas (CD95) and Fas ligand (FasL/CD95L) are involved in programmed cell deat h and the regulation of host immune responses. Fast has been shown to provi de immune privilege, thus prolonging the survival of unmatched grafts in a variety of tissues, such as eyes and testis. In murine Fast (mFasL) transge nic mice, Fast provoked granulocyte infiltration and insulitis in the pancr eas. We intended to study whether the expression of human Fast, instead of mFasL, on mouse beta islet cells could avoid granulocyte infiltration, and whether islet cells transgenic for Fast could be used in islet transplantat ion. We produced transgenic mice in which the human Fast transgene was driv en by rat insulin promoter and was expressed exclusively in the pancreas is let cells in ICR mice. In contrast to mFasL transgenic mice, histochemical staining showed that the pancreas was intact in human Fast transgenic ICR m ice. However, when human Fast transgenic islet cells were transplanted into allogeneic mice with streptozotocin-induced diabetes, human Fast appeared not to prolong graft survival. Intensive granulocyte infiltration into the islet grafts was observed in recipients (Balb/c mice) which received islet grafts from human Fast transgenic mice, but not from nontransgenic, allogen eic ICR mice on day 31. Our observations suggest that Fast alone is insuffi cient to confer immune protection, and that other environmental factors mig ht contribute to the formation of immune privilege sites in vivo Copyright (C) 2001 National Science Council, ROC and S. Karger AG, Basel.