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

¹ Research Division, Wills Eye Hospital, Philadelphia, PA, USA
² Federal University of São Paulo (UNIFESP), Brazil
³ Department of Ophthalmology, University of Nottingham, UK
⁴ National Institute of Health, Bethesda, MD, USA
⁵ University of São Paulo and Fund E J Zerbini, Brazil

Correspondence to:
Correspondence to:
Professor H S Dua
Division of Ophthalmology and Visual Sciences, B Floor, Eye, Ear, Nose and Throat Centre, Queens Medical Centre, University Hospital, Nottingham NG7 2UH, UK; harminder.dua{at}nottingham.ac.uk

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.

Keywords: cornea; conjunctiva; epithelium; lymphocyte; human mucosal lymphocyte antigen

Abbreviations: CALT, conjunctiva associated lymphoid tissue; HML-1, human mucosal lymphocyte antigen; IELs, intraepithelial lymphocytes; MALT, mucosa associated lymphoid tissue; TGF-ß, transforming growth factor beta

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