Ocular surface epithelium induces expression of human mucosal lymphocyte antigen (HML-1) on peripheral blood lymphocytes

Abstract

Background/aims: Peripheral blood CD8+ lymphocytes that home to mucosal surfaces express the human mucosal lymphocyte antigen (HML-1). At mucosal surfaces, including the ocular surface, only intraepithelial CD8+ lymphocytes express HML-1. These lymphocytes are retained in the intraepithelial compartment by virtue of the interaction between HML-1 and its natural ligand, E-cadherin, which is expressed on epithelial cells. The purpose of this study was to determine whether ocular surface epithelial cells (ocular mucosa) could induce the expression of human mucosal lymphocyte antigen on peripheral blood lymphocytes. Methods: Human corneal and conjunctival epithelial cells were co-cultured with peripheral blood lymphocytes. Both non-activated and activated lymphocytes were used in the experiments. After 7 days of incubation, lymphocytes were recovered and analysed for the antigens CD8/HML-1, CD4/HML-1, CD3/ CD8, CD3/CD4, CD3/CD25, CD8/CD25, and CD4/CD25 by flowcytometry. Results: Significant statistical differences were observed in the CD8/HML-1 expression when conjunctival epithelial cells were co-cultured with non-activated and activated lymphocytes (p = 0.04 for each) and when corneal epithelial cells were co-cultured with non-activated lymphocytes (p = 0.03). Significant statistical difference in CD4/HML-1 expression was observed only when conjunctival epithelial cells were co-cultured with activated lymphocytes (p = 0.02). Conclusion: Ocular surface epithelial cells can induce the expression of human mucosal lymphocyte antigen on CD8+ (and to some extent on CD4+) lymphocytes. This may allow the retention of CD8+ and CD4+ lymphocytes within the epithelial compartment of the conjunctiva and play a part in mucosal homing of lymphocytes.

Kinetics of immune cell migration at the human ocular surface

“…Studies on ocular surface disease such as ocular cicatricial pemphigoid have demonstrated that the ratio of CD8/HML-1 did not change, whereas in conjunctival carcinoma in situ, the ratio was decreased 3. This supports the suggestion that HML-1 is not induced on CD8+ T cells in inflammatory conditions, and its increase in neoplastic conditions of the epithelium is likely to be due to increased proliferation of IELs or due to induced expression by proliferating epithelial cells 23 24…”

“…HML-1 (CD103) is an αEβ7 integrin that binds to the ligand E-Cadherin, which is found on all epithelial layers of the conjunctiva and gut mucosa 7. Although HML-1 antigen is restricted primarily to IELs, its expression can be induced on T cells by exposure to various antigens and mitogens, and to cultured human corneal and conjunctival epithelial cells 23 24. In our study, the total percentage of CD3+ T cells that expressed HML-1 was low at around 8%.…”

Functional Foxp3+CD4+CD25(Bright+)“Natural” Regulatory T Cells Are Abundant in Rabbit Conjunctiva and Suppress Virus-Specific CD4+and CD8+Effector T Cells during Ocular Herpes Infection

“…Results from the present study may also suggest that among the circulating CD4 ϩ T cells, a dominant portion that naturally expresses the CD25 molecule is retained and survives in the conjunctival tissue by yet-to-be-defined mechanisms. It has also been shown that human conjunctival epithelial cells can induce the expression of human mucosal lymphocyte antigen 1 on CD4 ϩ T cells (31). These cells are retained in the intraepithelial compartment of the conjunctiva by virtue of the interaction between human mucosal lymphocyte antigen 1 and its natural ligand, E-cadherin, expressed on epithelial cells (31).…”

“…It has also been shown that human conjunctival epithelial cells can induce the expression of human mucosal lymphocyte antigen 1 on CD4 ϩ T cells (31). These cells are retained in the intraepithelial compartment of the conjunctiva by virtue of the interaction between human mucosal lymphocyte antigen 1 and its natural ligand, E-cadherin, expressed on epithelial cells (31). Suffia and coworkers recently showed a critical role for the ␣ E chain (CD103) of ␣ E ␤ 7 in the retention of CD4 ϩ CD25 ϩ T reg cells at mucocutaneous sites of inflammation (73).…”

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].…”