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 expres s Fas ligand (FasL) and may protect themselves by inducing apoptosis o f infiltrating inflammatory cells. We asked whether the Fas/FasL inter action could be used to protect a xenograft from rejection. We propose d that endothelial cells that are resistant to Fas-mediated killing co uld be considered as a vehicle for expression of recombinant FasL. Met hods. Based on the tetracycline-regulated expression system, construct s were designed that allow endothelial cell-specific and regulated exp ression of FasL by placing the tetracycline-dependent transactivator u nder control of the murine intercellular adhesion molecule-2 promoter. Results. Primary bovine endothelial cells transfected with FasL effic iently killed Fas-expressing cells in a regulated manner. Not only Fas -positive cell lines but also human peripheral blood lymphocytes under went apoptosis upon exposure to FasL-transfected endothelial cells. Co nclusion. This in vitro model may provide tools for the generation of transgenic animals to be used as donors for vascularized xenograft tra nsplantation.