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 death and the regulation of host immune responses. Fast has been shown to provide immune privilege, thus prolonging the survival of unmatched grafts in a variety of tissues, such as eyes and testis. In murine Fast (mFasL) transgenic mice, Fast provoked granulocyte infiltration and insulitis in the pancreas. 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 transplantation. We produced transgenic mice in which the human Fast transgene was driven by rat insulin promoter and was expressed exclusively in the pancreas islet cells in ICR mice. In contrast to mFasL transgenic mice, histochemical staining showed that the pancreas was intact in human Fast transgenic ICR mice. 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, allogeneic ICR mice on day 31. Our observations suggest that Fast alone is insufficient to confer immune protection, and that other environmental factors might contribute to the formation of immune privilege sites in vivo Copyright (C) 2001 National Science Council, ROC and S. Karger AG, Basel.