Research Group
- Prof. Michel Goldman, Principal Investigator
- Dr. Véronique Flamand, Research Associate
Location
- Université Libre de Bruxelles, Bruxelles, Belgium
Title
- Dendritic Cells Transduced with the FasL Gene as a Tool to Regulate Allograft Immunity
There is growing evidence that the induction of tolerance to organ transplants will require the infusion of donor cells endowed with tolerogenic properties. Along this line, it has been suggested that donor-type dendritic cells expressing the death-inducing molecule Fas-ligand (FasL) might selectively eliminate the recipient's T cells responsible for transplant rejection.
In preliminary experiments, we found that dendritic cells genetically engineered to overexpress FasL rapidly died unless they are deficient in Fas, the molecule which transmits the death signal inside the cell. When Fas-deficient dendritic cells overexpressing FasL were obtained, we observed that although these cells were endowed with killing properties they induce strong inflammation at the site of injection and promote efficient T cell responses.
The purpose of this project is to delineate the conditions that allow dissociation of the inflammatory reaction elicited by dendritic cells overexpressing FasL from their capacity to kill T cells specific for alloantigens expressed at their membrane. The data that will be generated should provide a better understanding of the links between inflammation/innate immunity and adaptive immune responses leading to transplant rejection. Hopefully, they will also lead to new cell therapy approaches for the induction of transplantation tolerance.
