Allergic Contact Dermatitis: How To Re-Induce Tolerance

Allergic contact dermatitis (ACD) is a skin inflammatory disease mediated by activation of CD8(+) cytotoxic T cells specific for haptens in contact with the skin. CD4(+) T cells behave as both regulatory and tolerogenic cells since they down-regulate the skin inflammation in patients with ACD (regulation) and prevent the developement of eczema (tolerance) in normal individuals. Thus, ACD corresponds to a breakdown of immune tolerance to haptens in contact with the skin. Several regulatory CD4(+) T cell subsets (Treg), especially CD4(+)CD25(+) natural Treg cells, are involved in immunological tolerance and regulation to haptens through the production of the immunosuppressive cytokines IL-10 and TGF-beta. Ongoing strategies to re-induce immune tolerance to haptens in patients with eczema include improvement of existing methods of tolerance induction (oral tolerance, low dose tolerance, allergen-specific immunotherapy, UV-induced tolerance) as well as development of new drugs able to activate IL-10 producing Treg cells in vivo. Ongoing and future progress in this area will open up new avenues for treatment of eczema and more generally autoimmune and allergic diseases resulting from Q breakdown of tolerance to autoantigens and allergens, respectively.