title: T-cell proliferation to superantigen-releasing Staphylococcus aureus by MHC class II-bearing keratinocytes under protection from bacterial cytolysin.
abstract: Skin colonization with Staphylococcus aureus may exacerbate skin disorders by activation of lesional T cells with release of superantigens. Although T cells are effectively stimulated by staphylococcal superantigens in the presence of epidermal accessory cells, it remains to be elucidated whether in vivo cutaneous colonization with S. aureus can activate T cells. We examined how T cells are stimulated in the presence of keratinocytes by mitomycin C (MMC)-treated S. aureus that are unable to propagate but retain their ability to produce superantigens. Peripheral blood mononuclear cells (PBMCs) proliferated well in response to MMC-treated superantigen-producing S. aureus and bacterial supernatants. When purified T cells were cultured with MMC-treated S. aureus or supernatant in the presence of interferon-gamma-pre-treated keratinocytes, the supernatant, but not MMC-treated S. aureus, stimulated T cells. MMC-treated S. aureus had a cytotoxic effect on keratinocytes. Furthermore, keratinocytes were highly susceptible to alpha-toxin compared with monocytes and B cells functioning as accessory cells in PBMCs. This suggests that a lack of response of T cells to S. aureus plus keratinocytes is due to damage of superantigen-presenting function of keratinocytes by cytolysin. The activity of alpha-toxin was much less stable than that of superantigen during incubation. Given that S. aureus-colonized skin provides circumstances in which viable keratinocytes are exposed to superantigens but not to active cytolysin(s), skin-infiltrating T cells may be effectively stimulated by S. aureus.
authors.affiliation: Department of Dermatology, Hamamatsu University School of Medicine, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Tokura
authors.forename: F
authors.initials: F
authors.lastname: Furukawa
authors.forename: H
authors.initials: H
authors.lastname: Wakita
authors.forename: H
authors.initials: H
authors.lastname: Yagi
authors.forename: T
authors.initials: T
authors.lastname: Ushijima
authors.forename: M
authors.initials: M
authors.lastname: Takigawa
mesh_terms: D000328:Adult; D002455:Cell Division / Q000187:drug effects; D003603:Cytotoxins / Q000096:biosynthesis; D004269:DNA, Bacterial / Q000096:biosynthesis; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000032:analysis*; D006801:Humans; D015603:Keratinocytes / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D016685:Mitomycin / Q000494:pharmacology; D009113:Muramidase / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018089:Superantigens / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D003603:Cytotoxins; D004269:DNA, Bacterial; D000949:Histocompatibility Antigens Class II; D018089:Superantigens; D016685:Mitomycin; D009113:Muramidase