Mechanisms of binding of cutaneous lymphocyte-associated antigen-positive and alpha e beta 7-positive lymphocytes to oral and skin keratinocytes

Intraepithelial lymphocytes (IEL) utilize the integrin alpha e beta 7 on th eir surface to bind to E-cadherin on epithelial cells in the gut and breast . In oral mucosa and skin IEL express alpha e beta 7 and the cutaneous lymp hocyte-associated antigen (CLA) but the mechanisms of adhesion of these sub sets to keratinocytes are unknown. Levels of alpha e beta 7 and CLA were up -regulated on peripheral blood lymphocytes (PBL) by transforming growth fac tor-beta (TGF-beta) and interleukin-12 (IL-12), respectively, and both grou ps of lymphocytes adhered onto oral and skin keratinocytes. Adhesion of IL- 12-activated PBL was totally abolished by anti-lymphocyte-associated functi on antigen type I (anti-LFA-1) antibodies but was unaffected by anti-alpha e beta 7 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-beta-activated PBL to E-cadherin-positive oral and ski n keratinocytes was partially inhibited by anti-alpha e beta 7 antibodies b ut was unaffected by the blocking antibody E4.6 against E-cadherin which de tects the binding site for alpha e beta 7-positive lymphocytes in breast an d gut epithelium. TGF-beta-activated PBL also bound to an E-cadherin-negati ve oral keratinocyte cell line and adhesion was inhibited by anti-alpha e b eta 7 antibodies. These results strongly suggest that in oral epithelium an d epidermis alpha e beta 7-positive lymphocytes do not bind to E-cadherin a nd there may be a novel second ligand for the alpha e beta 7 integrin.