Chemical activation of innate and specific immunity in contact dermatitis

Recent reports have suggested that chemical-induced allergic contact dermat itis may not be a traditional type IV hypersensitivity, in part due to the dual irritant and antigenic properties of sensitizing chemicals. In order t o investigate the contribution of these properties to the molecular and cel lular mechanism underlying allergic contact dermatitis, we evaluated oxazol one-induced changes in cell populations and cytokine production in the derm is of transgenic mice with impaired innate immunity (the Fc gamma R subunit knockout mouse), and absent specific immunity (the athymic mouse), and the appropriate B6,129F2 and C57BL/6 control mice. Oxazolone and croton oil we re applied in a single sensitizing dose, or in sensitizing and challenge do ses, and the dermal response was evaluated by immunohistochemistry. In the wild type mice, with or without sensitization to oxazolone or croton oil, w e observed mixed Th1/Th2 cytokine production and both CD4(+) and CD8(+) T l ymphocytes; however, the neutrophil was the predominant cell in the dermis, even 72 h after final chemical application. Athymic mice displayed a simil ar neutrophil response with moderate Th1/Th2 cytokine production, and Fc ga mma R subunit knockout mice exhibited very mild dermatitis when treated wit h either oxazolone or croton oil. These results provide support for the hyp othesis that allergic contact dermatitis is not a classic delayed type hype rsensitivity, demonstrate the importance of the interaction between the irr itant and antigenic properties of sensitizing chemicals in the development of allergic contact dermatitis, and suggest that the irritant effect of che micals may be mediated through the cutaneous innate immune system.