title: Accessory cell function of keratinocytes for superantigens. Dependence on lymphocyte function-associated antigen-1/intercellular adhesion molecule-1 interaction.
abstract: A growing body of evidence points to a role for epidermal keratinocytes as active participants in immunologic reactions. Inasmuch as certain T cell-mediated skin diseases, such as psoriasis and atopic dermatitis, are triggered by microbial infection, we asked whether multipassaged human keratinocytes could provide the costimulatory signals necessary to induce autologous T cell proliferation in response to bacterial-derived super-antigens. On exposure to IFN-gamma, keratinocytes are induced to express HLA-DR and HLA-DQ class II MHC Ag, and the lymphocyte function-associated Ag-1 counter-receptor intercellular adhesion molecule-1 (ICAM-1). This change in keratinocyte phenotype is accompanied by the ability of these cells to support T cell proliferation induced by two different bacterial-derived superantigens, staphylococcal enterotoxins A and B. Superantigen-driven proliferation in the presence of IFN-gamma-treated keratinocytes was significantly inhibited (70-90% reduction) by mAb against the LFA-1 alpha- or beta-chain or ICAM-1. Proliferation was not inhibited by mAb against the CD28 ligands BB-1 or B7, even though these keratinocytes express BB-1. In addition to previous defined roles for class II MHC Ag, stimulation of LFA-1 on the T cells by ICAM-1 on the keratinocytes also plays an important costimulatory role in this superantigen-mediated response. The accessory cell capability of keratinocytes was not unique to superantigen driven responses as PHA, as well as anti-CD3 mAb also induced vigorous T cell proliferation when IFN-gamma-treated keratinocytes were added. However, IFN-gamma-treated keratinocytes consistently failed to provoke an allogeneic response. These data demonstrate that 1) keratinocytes can serve as accessory cells for T cell proliferation using a variety of different stimuli, 2) the LFA-1/ICAM-1 interaction plays a major role in keratinocyte-mediated costimulation, and 3) previous reports in which IFN-gamma-treated keratinocytes failed to support T cell proliferation to nominal or alloantigens, may reflect impaired Ag presentation via class II MHC molecules, rather than lack of necessary costimulatory signals. These findings highlighting the accessory cell function of keratinocytes may have implications for our understanding of the pathogenesis of immunologic disorders of the skin.
authors.affiliation: Department of Pathology, University of Michigan, Ann Arbor 48109-0755.
authors.forename: B J
authors.initials: BJ
authors.lastname: Nickoloff
authors.forename: R S
authors.initials: RS
authors.lastname: Mitra
authors.forename: J
authors.initials: J
authors.lastname: Green
authors.forename: X G
authors.initials: XG
authors.lastname: Zheng
authors.forename: Y
authors.initials: Y
authors.lastname: Shimizu
authors.forename: C
authors.initials: C
authors.lastname: Thompson
authors.forename: L A
authors.initials: LA
authors.lastname: Turka
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000938:Antigen-Presenting Cells / Q000276:immunology*; D000941:Antigens / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D006801:Humans; D007399:Interphase / Q000276:immunology; D007519:Isoantigens / Q000235:genetics / Q000502:physiology; D015603:Keratinocytes / Q000276:immunology*; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology; D010835:Phytohemagglutinins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000941:Antigens; D000942:Antigens, Bacterial; D017252:CD3 Complex; D007519:Isoantigens; D016169:Lymphocyte Function-Associated Antigen-1; D010835:Phytohemagglutinins