Mechanisms of binding of cutaneous lymphocyte‐associated antigen‐positive and αeβ7‐positive lymphocytes to oral and skin keratinocytes

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Abstract
Intraepithelial lymphocytes (IEL) utilize the integrin αeβ7 on their surface to bind to E‐cadherin on epithelial cells in the gut and breast. In oral mucosa and skin IEL express αeβ7 and the cutaneous lymphocyte‐associated antigen (CLA) but the mechanisms of adhesion of these subsets to keratinocytes are unknown. Levels of αeβ7 and CLA were up‐regulated on peripheral blood lymphocytes (PBL) by transforming growth factor‐β (TGF‐β) and interleukin‐12 (IL‐12), respectively, and both groups of lymphocytes adhered onto oral and skin keratinocytes. Adhesion of IL‐12‐activated PBL was totally abolished by anti‐lymphocyte‐associated function antigen type 1 (anti‐LFA‐1) antibodies but was unaffected by anti‐αeβ7 antibodies indicating that adhesion of the CLA‐positive subset is mediated via LFA‐1 interaction with intercellular adhesion molecule‐1 (ICAM‐1). Adhesion of TGF‐β‐activated PBL to E‐cadherin‐positive oral and skin keratinocytes was partially inhibited by anti‐αeβ7 antibodies but was unaffected by the blocking antibody E4.6 against E‐cadherin which detects the binding site for αeβ7‐positive lymphocytes in breast and gut epithelium. TGF‐β‐activated PBL also bound to an E‐cadherin‐negative oral keratinocyte cell line and adhesion was inhibited by anti‐αeβ7 antibodies. These results strongly suggest that in oral epithelium and epidermis αeβ7‐positive lymphocytes do not bind to E‐cadherin and there may be a novel second ligand for the αeβ7 integrin.

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