Immunoregulation of allergic contact dermatitis

Allergic contact dermatitis (ACD) to haptens can serve as a valuable paradigm for understanding the physiopathology of T cell mediated immune responses. In sensitized individuals, exposure to the relevant hapten initiates clinical expression of ACD, which depends on the rapid activation of specific T cells. Mechanisms of tissue damage include direct cytotoxicity against keratinocytes, mostly mediated by CD8(+) T cells, and T cell release of cytokines, which amplify the inflammatory response by targeting resident skin cells. The expression of ACD is actively regulated by specialized subsets of T lymphocytes with suppressive functions. In particular, T regulatory cells producing high levels of IL-10 suppress ACD by blocking the functions of dendritic cells. In contrast CD4(+)CD25(+) regulatory T cells prevent immunopathological reactions and maintain peripheral tolerance to haptens by acting via a cell-to-cell contact mechanism. Understanding the role of suppressor T cells and the requirements for their in vivo and in vitro expansion are critical steps for the development of specific desensitization protocols in hapten-allergic individuals. This information may also provide the basis for novel interventions in other immune-mediated diseases.