Role of regulatory T cells in the induction of atopic dermatitis by immunosuppressive chemicals.

Immunosuppressive environmental chemicals may exacerbate allergic diseases, including atopic dermatitis (AD). We examined the effects of the immunosuppressive environmental chemicals methoxychlor, parathion, piperonyl butoxide, dexamethasone, and cyclophosphamide on picryl-chloride-induced AD in NC/Nga mice. Mice were orally exposed (age, 5 weeks) to these chemicals; during their sensitization and challenge (age, 8-12 weeks) with picryl chloride, we measured ear thickness and scored skin dryness, erythema, edema, and wounding. After the challenge, we analyzed dermatitis severity and cytokine gene expression in the pinna, serum levels of IgE and IgG2a, T- and B-cell numbers and cytokine production in auricular lymph nodes, and counted splenic regulatory T cells. Exposure to environmental immunosuppressive chemicals markedly increased dermatitis severity and gene expression in the pinna; serum IgE and IgG2a levels; and numbers of helper T cells and IgE-positive B cells, production of Th1 and Th2 cytokines, and production of IgE in auricular lymph-node cells and markedly decreased the numbers of splenic regulatory T cells. Prior exposure to immunosuppressive environmental chemicals aggravates AD; a decrease in the numbers of regulatory T cells may influence this process.