Ectopic expression of Fas Ligand on cardiomyocytes renders cardiac allografts resistant to CD4+ T-cell mediated rejection

• We over-expressed Fas Ligand on donor cardiomyocytes.
• We investigated if this ectopic expression could prolong cardiac graft survival.
• FasL was incapable of prolonging grafts in fully immunocompetent recipients.
• FasL was capable of prolonging grafts when exposed to CD4+ T-cells.

Fas Ligand limits inflammatory injury and permits allograft survival by inducing apoptosis of Fas-bearing lymphocytes. Previous studies have shown that the CD4+ T-cell is both sufficient and required for murine cardiac allograft rejection. Here, utilizing a transgenic mouse that over-expresses Fas Ligand specifically on cardiomyocytes as heart donors, we sought to determine if Fas Ligand on graft parenchymal cells could resist CD4+ T-cell mediated rejection. When transplanted into fully immunocompetent BALB/c recipients Fas Ligand transgenic hearts were acutely rejected. However, when transplanted into CD4+ T-cell reconstituted BALB/c-rag−/− recipients, Fas Ligand hearts demonstrated long-term survival. These results indicate that Fas Ligand over-expression on cardiomyocytes can indeed resist CD4+ T-cell mediated cardiac rejection and suggests contact dependence between Fas Ligand expressing graft parenchymal cells and the effector CD4+ T-cells.