An obligate role for T-cell receptor αβ+ T cells but not T-cell receptor γδ+ T cells, B cells, or CD40/CD4OL interactions in a mouse model of atopic dermatitis

Abstract

Background: We recently described a murine model of atopic dermatitis (AD) elicited by epicutaneous sensitization with ovalbumin (OVA). The skin lesions in these mice were characterized by a dermal infiltrate consisting of eosinophiis and T cells and by increased expression of the TH2 cytokines IL-4 and IL-5. Epicutaneous sensitization induces a rise in the levels of serum total IgE and OVA-specific antibodies, further indicating that it elicits a predominantly TH2 response. Objective: This study was undertaken to assess the roles of T cells, B cells, and CD4OL-CD40 interactions in AD. Methods: Mice with targeted gene deletions were sensitized with OVA. Histologic and immunohistochemical examinations, as well as measurements of IL-4 mRNA, were performed on OVA-sensitized skin. Total and antigen-specific serum IgE levels were determined. Results: RAG2−/− mice, which lack both T and B cells, did not exhibit cellular infiltration, induction of dermal IL-4 mRNA, or elevation of serum IgE after OVA sensitization; all of these features were present in B-cell-deficient IgH−/− mice. T-cell receptor α−/− mice did not display cellular infiltration, IL-4 mRNA expression, or increased IgE levels after OVA sensitization, but these responses were elicited in T-cell receptor δ−/− mice after sensitization. Absence of CD40 had no effect on these responses. Conclusion: These results suggest that αβ T cells, but not γδ T cells, B cells, or CD40L-CD40 interactions, are critical for skin inflammation and the TH2 response in AD.