title: Regulated and endothelial cell-specific expression of Fas ligand: an in vitro model for a strategy aiming at inhibiting xenograft rejection.
abstract: BACKGROUND
  Immunologically privileged sites have been shown to express Fas ligand (FasL) and may protect themselves by inducing apoptosis of infiltrating inflammatory cells. We asked whether the Fas/FasL interaction could be used to protect a xenograft from rejection. We proposed that endothelial cells that are resistant to Fas-mediated killing could be considered as a vehicle for expression of recombinant FasL.
  
  
  METHODS
  Based on the tetracycline-regulated expression system, constructs were designed that allow endothelial cell-specific and regulated expression of FasL by placing the tetracycline-dependent transactivator under control of the murine intercellular adhesion molecule-2 promoter.
  
  
  RESULTS
  Primary bovine endothelial cells transfected with FasL efficiently killed Fas-expressing cells in a regulated manner. Not only Fas-positive cell lines but also human peripheral blood lymphocytes underwent apoptosis upon exposure to FasL-transfected endothelial cells.
  
  
  CONCLUSIONS
  This in vitro model may provide tools for the generation of transgenic animals to be used as donors for vascularized xenograft transplantation.
authors.affiliation: Sandoz Center for Immunobiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA. hien.tran@rzmail.uni-erlangen.de
authors.forename: T H
authors.initials: TH
authors.lastname: Tran
authors.forename: S
authors.initials: S
authors.lastname: Grey
authors.forename: J
authors.initials: J
authors.lastname: Anrather
authors.forename: F
authors.initials: F
authors.lastname: Steinhäuslin
authors.forename: F H
authors.initials: FH
authors.lastname: Bach
authors.forename: H
authors.initials: H
authors.lastname: Winkler
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology; D017209:Apoptosis; D002417:Cattle; D016923:Cell Death; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism*; D053222:Fas Ligand Protein; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D019169:Jurkat Cells / Q000502:physiology; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D018448:Models, Immunological
chemical_list: C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins