An obligate role for T-cell receptor alpha beta T+ cells but not T-cell receptor gamma delta T+ cells, B cells, or CD40/CD40L interactions in a mousemodel of atopic dermatitis

Background: We recently described a murine model of atopic dermatitis (AD) elicited by epicutaneous sensitization with ovalbumin (OVA). The skin lesio ns in these mice were characterized by a dermal infiltrate consisting of eo sinophils and T cells and by increased expression of the T(H)2 cytokines IL -4 and IL-5. Epicutaneous sensitization induces a rise in the levels of ser um total IgE and OVA-specific antibodies, further indicating that it elicit s a predominantly T(H)2 response. Objective: This study was undertaken to assess the roles of T cells, B cell s, and CD40L-CD40 interactions in AD. Methods: Mice with targeted gene deletions were sensitized with OVA. Histol ogic and immunohistochemical examinations, as well as measurements of IL-4 mRNA, were performed on OVA-sensitized skin. Total and antigen-specific ser um IgE levels were determined. Results: RAG2(-/-) mice, which lack both T and B cells, did not exhibit cel lular infiltration, induction of dermal IL-4 mRNA, or elevation of serum Ig E after OVA sensitization: all of these features were present in B-cell-def icient IgH(-/-) mice. T-cell receptor alpha (-/-) mice did not display cell ular infiltration, IL-4 mRNA expression, or increased IgE levels after OVA sensitization, but these responses were elicited in T-cell receptor delta ( -/-) mice after sensitization. Absence of CD40 had no effect on these respo nses. Conclusion: These results suggest that alpha beta T cells, but not gamma de lta T cells, B cells, or CD40L-CD40 interactions, are critical for skin inf lammation and the T(H)2 response in AD.