PURPOSE. To determine the extent to which CD95 ligand (CD95L) expressed on corneal epithelium and endothelium influences survival of cornea grafts placed orthotopically and heterotopically in the anterior chamber (AC), an immune-privileged site. METHODS. Corneas from eyes of C57BL/6 (B6) and B6.gld (CD95L deficient) mice were (1) rendered into small full-thickness fragments, with or without an epithelial layer, and placed behind recipient corneas in the ACs of BALB/c eyes, while BALB/c corneas were similarly implanted in eyes of B6 and B6.lpr (CD95 deficient) mice; or (2) corneas were grafted orthotopically in BALB/c eyes as intact corneas or as composite corneas in which epithelium from one donor source was layered in vitro onto epithelium-deprived stroma+endothelium from another donor source before grafting. The fate of the grafts was assessed clinically and histologically, and the capacity of the grafts to sensitize recipient mice to donor alloantigens (delayed hypersensitivity, DH) was evaluated. RESULTS. Allogeneic, full-thickness B6.gld corneal fragment grafts placed in the AC of BALB/c mice were rejected and sensitized their recipients, whereas epithelium-deprived B6.gld cornea fragments survived indefinitely and failed to sensitize their recipients. BALB/c corneal fragment grafts placed in the AC of C57BL/6 or B6.lpr eyes were rejected. Orthotopic cornea grafts composed of B6.gld epithelium layered onto wild-type B6 stroma and endothelium were rejected at a tempo and incidence similar to full-thickness B6 grafts, whereas orthotopic composite cornea grafts containing B6 epithelium layered onto B6.gld stroma+endothelium were vigorously rejected. CONCLUSIONS. CD95L expression on epithelium of full-thickness cornea fragment grafts placed in the anterior chamber of BALB/c eyes protects these heterotopic grafts from rejection but has only a trivial role to play in determining the fate of orthotopic corneal grafts. In the latter type of corneal grafts, CD95L expression on the endothelium plays an essential role in preventing graft rejection.
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