CD95 LIGAND (FASL)-INDUCED APOPTOSIS IS NECESSARY FOR CORNEAL ALLOGRAFT SURVIVAL

Although anatomical barriers and soluble mediators have been implicate d in immune privilege, it appears that the apoptotic cell death of Fas (+) cells by tissue-associated CD95 ligand (Fas ligand, Fast) is an im portant component. One clinical example of the function of an immune p rivileged site is the success of human corneal transplants, where a ve ry high percentage of transplants accept without tissue matching or im munosuppressive therapy. Since the mouse cornea expresses abundant Fas ligand and immune privilege has been implicated in the success of the se transplants, we examined the role of Fast in corneal transplantatio n Our results show that human corneas express functional Fast capable of killing Fas(+) lymphoid cells in an in vitro culture system. Using a mouse model for corneal allograft transplantation, FasL(+) orthograf ts were accepted at a rate of 45%, whereas FasL(-) grafts, or normal g rafts transplanted to Fas(-) mice, were rejected 100% of the time. His tological analysis found that FasL(+) grafts contained apoptotic monon uclear cells indicating the induction of apoptosis by the graft, while rejecting FasL(-) corneas contained numerous inflammatory cells witho ut associated apoptosis. Taken together our results demonstrate that F ast expression on the cornea is a major factor in corneal allograft su rvival and, thus, we provide an explanation for one of the most succes sful tissue transplants performed in humans.