Immune Privilege and Immunogenicity Reside among Different Layers of the Mouse Cornea

Abstract

Purpose: To determine the extent to which each layer of the mouse cornea displays alloimmuno-genicity or immune privilege. Methods: Intact corneas or individual or combined layers of corneas from normal or cauterized eyes of BALB/c, C57BL/6, and CD95L-deficient B6-gld mice were grafted beneath the kidney capsule of normal BALB/c, B10.D2, BALB.B mice or of BALB/c mice presensitized to donor antigens. Graft fate was assessed 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 rejected acutely. Similar results were obtained with allografts of corneal epithelium alone (if supported by syngeneic viable stroma), allografts of epithelium from cauterized corneas (containing Langerhans' cells), and stromal allografts deprived of endothelium. Grafts comprised of stroma plus endothelium (without epithelium) were not rejected, nor did they induce DH unless the graft had no CD95L expression. If stroma-endothelium grafts had no CD95L 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 not 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-expressing endothelium can inhibit the stroma from inducing immunity directed at MHC alloantigens, but in presensitized mice the endothelium can protect itself only from immune rejection.

Immune Cells on the Corneal Endothelium of an Allogeneic Corneal Transplantation Rabbit Model

“…[18][19][20][21][22][23][24] Numerous basic research studies have demonstrated that the immune privilege of the eye is not solely a phenomenon due to immunologic ignorance, but instead is a highly orchestrated immune system consisting of unique immune suppression mechanisms, widely known as anterior chamber-associated immune deviation. [21][22][23]25 This immuneprivileged environment, as well as the underlying mechanisms involved in corneal graft rejection by host immune systems, has also been intensively investigated.…”

“…Indeed, the use of reconstituted mouse corneal grafts confirmed that the corneal epithelium had a higher allosensitization potency when compared with endothelium. [35][36][37] By contrast, the incidence of graft rejection in DSEK, and even in DMEK, suggests that the corneal endothelium also has immunogenicity. Our current data for our rabbit DSEK model showed that immune cells migrated onto allogeneic graft corneal endothelium and expressed proinflammatory cytokines, as observed in PK.…”

Immune regulation and the eye

“…Furthermore, parts of the eye like the cornea are considered to be intrinsically immune privileged tissues because when transplanted to sites perfectly capable of rejecting foreign antigens, they enjoy acceptance. For instance, a cornea is accepted when transplanted under the kidney capsule, a site that is not immune privileged [5,6].…”

B7-H1-Induced Apoptosis as a Mechanism of Immune Privilege of Corneal Allografts

“…In addition, normal corneal endothelial cells constitutively express immune-modulating factors such as CD95L (28). Thus, corneal endothelium is considered to play a central role in the protection of corneal allografts from immunologic rejection when transplanted orthotopically in the eyes (29) and heterotopically beneath the kidney capsule (30,31). Molecular mechanisms of corneal invulnerability are not perfectly understood.…”