Expression of human Fas ligand on mouse beta islet cells does not induce insulitis but is insufficient to confer immune privilege for islet grafts
Journal
Journal of Biomedical Science
Journal Volume
8
Journal Issue
3
Pages
262-269
Date Issued
2001
Author(s)
Abstract
Fas (CD95) and Fas ligand (FasL/CD95L) are involved in programmed cell death and the regulation of host immune responses. FasL 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 FasL (mFasL) transgenic mice, FasL provoked granulocyte infiltration and insulitis in the pancreas. We intended to study whether the expression of human FasL, instead of mFasL, on mouse β islet cells could avoid granulocyte infiltration, and whether islet cells transgenic for FasL could be used in islet transplantation. We produced transgenic mice in which the human FasL 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 FasL transgenic ICR mice. However, when human FasL transgenic islet cells were transplanted into allogeneic mice with streptozotocin-induced diabetes, human FasL 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 FasL transgenic mice, but not from nontransgenic, allogeneic ICR mice on day 31. Our observations suggest that FasL alone is insufficient to confer immune protection, and that other environmental factors might contribute to the formation of immune privilege sites in vivo. Copyright ? 2001 National Science Council, ROC and S. Karger AG, Basel.
Subjects
β Islet cells; Human Fas ligand; Immune privilege; Murine allogeneic islet transplantation
SDGs
Other Subjects
FAS ligand; animal experiment; animal model; article; cell infiltration; controlled study; disease association; graft survival; granulocyte; immunomodulation; insulitis; mouse; nonhuman; pancreas islet transplantation; pathogenesis; priority journal; protein expression; streptozocin diabetes; Animals; Cell Death; Diabetes Mellitus, Experimental; Fas Ligand Protein; Graft Survival; Humans; Immune Tolerance; Inflammation; Insulin; Islets of Langerhans; Islets of Langerhans Transplantation; Jurkat Cells; Membrane Glycoproteins; Mice; Mice, Inbred Strains; Mice, Transgenic; Neutrophil Infiltration; Promoter Regions (Genetics); Rats; Reverse Transcriptase Polymerase Chain Reaction; Species Specificity; Transgenes; Murinae; Mus musculus
Type
journal article