Epithelium-deficient corneal allografts display immune privilege beneath the kidney capsule.
OBJECTIVE
To determine whether corneal tissue as an allograft displays immune privilege in a nonprivileged site and, if so, whether CD95 ligand expression contributes to the privileged status.


METHODS
Syngenic and allogeneic corneal tissues deprived of epithelium were transplanted beneath the kidney capsule of normal mice. Syngeneic BALB/c, allogeneic C57BL/6, and allogeneic B6Smn.C3H-gld (CD95 ligand-deficient) mice were used as donors for BALB/c recipients, and syngeneic C3H/HeJ-gld (CD95 ligand-deficient) mice were used for normal C3H/HeJ recipients. Allogeneic conjunctival segments served as positive grafting controls. Graft fate was assessed by visual inspection at 4, 7, 14, and 21 days and was confirmed by histologic study. Viability of graft endothelium was assessed by immunocytochemical analysis.


RESULTS
Syngeneic corneas and C57BL/6 corneas survived almost indefinitely beneath the kidney capsule. Both the stroma and the endothelial layers remained healthy and intact. Allogeneic conjunctiva evoked a strong inflammatory response attended by neovascularization. Similarly, B6-gld corneas deficient in CD95 ligand expression showed acute destruction beneath the kidney capsule. Circumstantial evidence implicates alloimmune rejection as the mechanism.


CONCLUSIONS
Epithelium-deprived corneas from normal mice possess inherent immune privilege that protects them from alloimmune rejection even at nonprivileged sites. Constitutive expression of CD95 ligand contributes to the privileged status. It is inferred that the extraordinary success of orthotopic corneal allografts owes as much to the qualities of the graft as an immune-privileged tissue as to the qualities of the eye as an immune-privileged site.
Hori
J
J
Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts 02114, USA.
Joyce
N
N
Streilein
J W
JW
D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D003315:Cornea / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016039:Corneal Transplantation / Q000276:immunology* / Q000473:pathology; D004728:Endothelium, Corneal / Q000378:metabolism / Q000473:pathology; D019573:Epithelium, Corneal / Q000276:immunology*; D053222:Fas Ligand Protein; D019084:Fluorescent Antibody Technique, Indirect; D006085:Graft Survival / Q000276:immunology; D007668:Kidney / Q000601:surgery*; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D016042:Transplantation, Heterotopic; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic
D015704:CD4 Antigens; D016827:CD8 Antigens; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D016177:Macrophage-1 Antigen; D008562:Membrane Glycoproteins