Regulated and endothelial cell-specific expression of Fas ligand: an in vitro model for a strategy aiming at inhibiting xenograft rejection.
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.
Tran
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TH
Sandoz Center for Immunobiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA. hien.tran@rzmail.uni-erlangen.de
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Anrather
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Steinhäuslin
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Bach
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Winkler
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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
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins