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Topical Superantigen Exposure Induces Epidermal Accumulation of CD8⁺ T Cells, a Mixed Th1/Th2-Type Dermatitis and Vigorous Production of IgE Antibodies in the Murine Model of Atopic Dermatitis¹

Terhi Savinko^*, Antti Lauerma, Sari Lehtimäki^*, Michael Gombert, Marja-Leena Majuri^*, Nanna Fyhrquist-Vanni^*, Marie-Caroline Dieu-Nosjean^¶, Lajos Kemeny^||, Henrik Wolff^,#, Bernhard Homey and Harri Alenius^2,*

^* Laboratory of Immunotoxicology, Section of Dermatology, and Laboratory of Pathology, Finnish Institute of Occupational Health, Helsinki, Finland; Department of Dermatology, Heinrich-Heine-University Düsseldorf, Germany; ^¶ Institut National de la Santé et de la Recherche Médicale Unité 255, Laboratoire d’Immunologie Cellulaire et Clinique, Centre de Recherches Biomedicales des Cordeliers, Paris, France; ^|| Department of Dermatology and Allergology, University of Szeged, Szeged, Hungary; and ^# Department of Pathology, Helsinki University Central Hospital, Helsinki, Finland

Patients with atopic dermatitis (AD) have repeated cutaneous exposure to both environmental allergens and superantigen-producing strains of Staphylococcus aureus. We used a murine model of AD to investigate the role of staphylococcal enterotoxin B (SEB) in the modulation of allergen-induced skin inflammation. Mice were topically exposed to SEB, OVA, a combination of OVA and SEB (OVA/SEB), or PBS. Topical SEB and OVA/SEB exposure induced epidermal accumulation of CD8⁺ T cells and TCRV8⁺ cells in contrast to OVA application, which induced a mainly dermal infiltration of CD4⁺ cells. SEB and OVA/SEB exposure elicited a mixed Th1/Th2-associated cytokine and chemokine expression profile within the skin. Restimulation of lymph node cells from OVA- and OVA/SEB-exposed mice with OVA elicited strong production of IL-13 protein, whereas substantial amounts of IFN- protein were detected after SEB stimulation of cells derived from SEB- or OVA/SEB-exposed mice. Topical SEB treatment elicited vigorous production of SEB-specific IgE and IgG2a Abs and significantly increased the production of OVA-specific IgE and IgG2a Abs. The present study shows that topical exposure to SEB provokes epidermal accumulation of CD8⁺ T cells, a mixed Th2/Th1 type dermatitis and vigorous production of specific IgE and IgG2a Abs, which can be related to the chronic phase of atopic skin inflammation.

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