E-cadherin distribution and epithelial basement membrane characteristics of the normal human conjunctiva and cornea

Abstract

The conjunctival mucosa has several similarities to the mucosal immune system of the gut and bronchus. Like the gut and bronchial mucosa, the conjunctiva is capable of inducing tolerance to encountered antigens and possesses a repertoire of CD8+ intraepithelial lymphocytes (IELs) bearing the human mucosal lymphocyte-1 antigen (HML-1) which has been shown to be an alpha E beta 7 integrin. The epithelial cells surface ligand for HML-1 is E-cadherin. The distribution of E-cadherin in the normal human conjunctiva and cornea is not known. We investigated E-cadherin distribution in the conjunctiva and cornea by immunohistochemistry. E-cadherin was found to be present in all layers of the conjunctival epithelium but not in corneal epithelium. In the conjunctiva it may act as a ligand for the HML-1+ IELs. The specific location of IELs along the basal cells of the conjunctiva compared with the generalised distribution of E-cadherin through all layers, indicates that factors other than E-cadherin binding determine the distribution of HML-1+ IELs. We performed electron microscopy on de-epithelialised conjunctival and corneal samples. We demonstrated the presence of epithelial basement membrane pores in the conjunctiva but not in the cornea. Lymphocyte migration from the substantia propria to the intraepithelial compartment appears to occur through these pores, which may also serve as a conduit for antigen presentation by epithelial antigen presenting cells (APCs) to lymphocytes in the substantia propria.

Human Conjunctiva Contains High Endothelial Venules That Express Lymphocyte Homing Receptors

“…HML-1 positive CD8jlymphocytes are also present in the acinar epithelium of the lacrimal gland. The presence of the HML-1 positive lymphocytes may be explained by the fact that the epithelium of the conjunctiva expresses the adhesion molecule E-cadherin (Scott et al, 1997), which is known to be the ligand for HML-1. The epithelium also contains a large number of antigen presenting, MHC class II positive Langerhans cells.…”

Defective E-cadherin/catenin complexes in human cancer

“…6. A heterophilic interaction between E-cad of the epithelial cells and α E β 7 integrin of lymphocytes is described in the conjunctiva and the lacrimal gland in patients with Sjögren's syndrome [92,249]. A pax-6 (paired box 6) knock-out mouse shows reduced R-cadherin, cadherin-6 and cadherin-8 expression in the brain and the eye, leading to a S(mall) E(ye) phenotype [32,288].…”

Regulation of Ocular Immune Responses by Corneal Epithelium

“…Another observation suggesting E 7 integrin involvement in Treg activity is that CD8+ E 7 intraepithelial lymphocytes (IELs) home to the ocular surface by their interaction with E-cadherin, which is found in the conjunctival epithelium. These findings show that these integrins possibly have a localizational role in their interactions with Tregs [46,[141][142][143][144].…”