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.