Epicutaneous sensitization with superantigen induces allergic skin inflammation

Background: Atopic dermatitis (AD) is characterized by skin infiltration with eosinophils and lymphocytes and expression of Th-2 cytokines in acute skin lesions. The skin of patients with AD is frequently colonized with enterotoxin-secreting strains of Staphylococcus aureus. Staphylococcal enterotoxins have been implicated in the exacerbations of the inflammatory skin lesions in patients with AD. Objective: We sought to determine whether epicutaneous (EC) sensitization of mice with staphylococcal enterotoxin B (SEB) results in allergic skin inflammation. Methods: BALB/c mice were EC-sensitized with SEB. Their skin was examined for allergic inflammation and cytokine expression, and their splenocytes were examined for cylokine secretion in response to SEB. Results: EC sensitization with SEB elicited a local, cutaneous, inflammatory response characterized by dermal infiltration with eosinophils and mononuclear cells and increased mRNA expression of the Th-2 cytokine IL-4 but not of the Th-1 cytokine IFN-gamma. EC-sensitized mice mounted a systemic Th-2 response to SEB evidenced by elevated total and SEB-specific IgG1 and IgE. Although EC sensitization with SEB resulted in selective depletion of SEB-specific T-cell receptor Vbeta8+ cells from the spleen and sensitized skin, splenoeytes from SEB-sensitized mice secreted relatively more IL-4 and less IFN-gamma than did saline-sensitized controls, consistent with Th-2 skewing of the systemic immune response to the superantigen. Conclusion: These results suggest that EC exposure to super-antigens skews the immune response toward Th-2 cells, leading to allergic skin inflammation and increased IgE synthesis that are characteristic of AD.