title: FasL-transfected endothelial cells decrease the proliferative response of allogeneic PBL.
abstract: Graft endothelium has a key role in organ transplantation because it regulates graft infiltration by allogeneic activated T cells. Overexpression of death molecules that could induce apoptosis of alloreactive T cells might be an alternative to the immunosuppressive treatment currently used in graft transplantation. Several studies have shown that immune-privileged sites express Fas ligand (FasL) and induce apoptosis of activated T-cells. We propose that endothelial cells engineered to express FasL could inhibit alloreactive T cell-proliferation by inducing apoptosis. An expression vector was constructed with human FasL cDNA and used to transfect an endothelial cell line (ECV304 cells). We demonstrated that FasL-transfected ECV304 cells were effective in inducing apoptosis of Jurkat T cell lymphoma as an agonist anti-Fas antibody. Using a mixed lymphocyte-endothelial cell culture model we observed that FasL-transfected ECV304 cells which conserved their two principal costimulatory pathways inhibited alloreactive T cell-proliferation by inducing activated T-cell apoptosis. These results suggest that endothelial cells could be interesting candidates to convey a death signal and induce hyporesponsiveness of alloreactive T cells during organ transplantation.
authors.affiliation: UPRES-EA 3249 Cellules Hématopoïétiques, Hémostase et Greffe, Faculté de Médecine, 2 bis boulevard Tonnelĺe 37032 Tours, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Cappellesso
authors.forename: Gilles
authors.initials: G
authors.lastname: Thibault
authors.forename: Cyrille
authors.initials: C
authors.lastname: Hoarau
authors.forename: Olivier
authors.initials: O
authors.lastname: Hérault
authors.forename: Sophie
authors.initials: S
authors.lastname: Iochmann
authors.forename: Pierre
authors.initials: P
authors.lastname: Bardos
authors.forename: Yvon
authors.initials: Y
authors.lastname: Lebranchu
mesh_terms: D017209:Apoptosis; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D004730:Endothelium, Vascular / Q000166:cytology* / Q000502:physiology; D053222:Fas Ligand Protein; D006801:Humans; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection
chemical_list: C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins