Regulated and endothelial cell-specific expression of Fas ligand: an in vitro model for a strategy aiming at inhibiting xenograft rejection
Tran, T.H.; Grey, S.; Anrather, J.; Steinhäuslin, F.; Bach, F.H.; Winkler, H.
Transplantation 66(9): 1126-1131
1998
ISSN/ISBN: 0041-1337 PMID: 9825805 Document Number: 489854
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 cells lines but also human peripheral blood lymphocytes underwent apoptosis upon exposure to FasL-transfected endothelial cells. Conclusion. This in vitro model may provide. tools for the generation of transgenic animals to be used as donors for vascularized xenograft transplantation.