FasL-transfected endothelial cells decrease the proliferative response of allogeneic PBL
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- 作者：Cappellesso ; Sandrine ; Thibault ; Gilles ; Hoarau ; Cyrille ; Hé ; rault ; Olivier ; Iochmann ; Sophie ; et. al.
- 关键词：Apoptosis ; Transplantation ; Tolerance/suppression ; 7-AAD ; 7-amino actinomycin D ; DC ; dendritic cells ; EC ; endothelial cells ; FasL ; Fas ligand ; MLEC ; mixed lymphocyte endothelial cell culture.
- 刊名：Transplant Immunology
- 出版年：2002
- 出版时间：November, 2002
- 年：2002
- 卷：10
- 期：4
- 页码：293-302
- 全文大小：299 K
文摘
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.