Immune privilege and immunogenicity reside among different layers of the mouse cornea

PURPOSE. To determine the extent to which each layer of the mouse cornea di splays alloimmunogenicity or immune privilege. METHODS. Intact corneas or individual or combined layers of corneas from no rmal or cauterized eyes of BALB/c. C57BL/b, and CD95L-deficient B6-gld mice were grafted beneath the kidney capsule of normal BALB/c, B10.D2, BALB.B m ice or of BALB/c mice presensitized to donor antigens. Graft fate was asses sed clinically and histologically and acquisition of donor-specific delayed hypersensitivity (DH) was assessed at selected intervals after grafting. RESULTS. Full-thickness allogeneic corneas induced vigorous DH and were rej ected acutely. Similar results were obtained with allografts of corneal epi thelium alone (if supported by syngeneic viable stroma), allografts of epit helium from cauterized corneas (containing Langerhans' cells), and stromal allografts deprived of endothelium. Grafts comprised of stroma plus endothe lium (without epithelium) were not rejected, nor did they induce DH unless the graft had no CD95L expression. if stroma- endothelium grafts had no CD9 5L expression, DH directed against major histocompatibility complex (MHC), but not minor histocompatibility, alloantigens was induced. Moreover, CD95L expressed on stroma- endothelium grafts protected endothelial cells, but n ot stromal cells, from rejection in presensitized recipients. CONCLUSIONS. When grafted to a heterotopic site, the alloimmunogenicity of the normal cornea resides within its epithelial and stromal layers, whereas immune privilege arises from the endothelium. In normal mice, CD95L-expres sing endothelium can inhibit the stroma from inducing immunity directed at MHC alloantigens, but in presensitized mice the endothelium can protect its elf only from immune rejection.