title: Mechanisms of binding of cutaneous lymphocyte-associated antigen-positive and alphaebeta7-positive lymphocytes to oral and skin keratinocytes.
abstract: Intraepithelial lymphocytes (IEL) utilize the integrin alphaebeta7 on their surface to bind to E-cadherin on epithelial cells in the gut and breast. In oral mucosa and skin IEL express alphaebeta7 and the cutaneous lymphocyte-associated antigen (CLA) but the mechanisms of adhesion of these subsets to keratinocytes are unknown. Levels of alphaebeta7 and CLA were up-regulated on peripheral blood lymphocytes (PBL) by transforming growth factor-beta (TGF-beta) 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-alphaebeta7 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 skin keratinocytes was partially inhibited by anti-alphaebeta7 antibodies but was unaffected by the blocking antibody E4.6 against E-cadherin which detects the binding site for alphaebeta7-positive lymphocytes in breast and gut epithelium. TGF-beta-activated PBL also bound to an E-cadherin-negative oral keratinocyte cell line and adhesion was inhibited by anti-alphaebeta7 antibodies. These results strongly suggest that in oral epithelium and epidermis alphaebeta7-positive lymphocytes do not bind to E-cadherin and there may be a novel second ligand for the alphaebeta7 integrin.
authors.affiliation: Department of Oral Pathology, St Bartholomew's & the Royal London School of Medicine and Dentistry, London, UK.
authors.forename: D W
authors.initials: DW
authors.lastname: Brown
authors.forename: J
authors.initials: J
authors.lastname: Furness
authors.forename: P M
authors.initials: PM
authors.lastname: Speight
authors.forename: G J
authors.initials: GJ
authors.lastname: Thomas
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: M H
authors.initials: MH
authors.lastname: Thornhill
authors.forename: P M
authors.initials: PM
authors.lastname: Farthing
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; D001665:Binding Sites; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion; D004797:Enzyme-Linked Immunosorbent Assay; D000078404:Epidermal Cells; D004817:Epidermis / Q000502:physiology*; D004847:Epithelial Cells / Q000502:physiology; D005434:Flow Cytometry; D006801:Humans; D016023:Integrins / Q000276:immunology / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D018664:Interleukin-12 / Q000494:pharmacology; D015603:Keratinocytes / Q000502:physiology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D008214:Lymphocytes / Q000276:immunology / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D009061:Mouth Mucosa / Q000166:cytology / Q000502:physiology*; D011485:Protein Binding; D051381:Rats; D016212:Transforming Growth Factor beta / Q000494:pharmacology
chemical_list: D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; C063419:CTAGE1 protein, human; D015820:Cadherins; D016023:Integrins; D016169:Lymphocyte Function-Associated Antigen-1; D008562:Membrane Glycoproteins; D016212:Transforming Growth Factor beta; C070709:integrin alphaEbeta7; D018799:Intercellular Adhesion Molecule-1; D018664:Interleukin-12