Atopic Dermatitis (A.D. is a chronic inflammatory skin disease of unknown etiology). However, the majority of patients with A.D. have abnormal immune function as evidenced by clinical observations of decreased cell mediated immunity and by elevated serum IgE levels. We have recently described a number of immunoregulatory abnormalities in patients with A.D. They include: 1) decreased cell mediated lympholysis (CML) against allogeneic cells; 2) decreased circulating T8+ suppressor/cytotoxic cells; 3) decreased autologous mixed lymphocyte reaction (AMLR); 4) presence of circulating mononuclear cells of T11+, M1+ phenotype which are cytotoxic to skin fibroblasts. We propose to investigate the mechanisms that underlie these abnormalities and to relate them to possible mechanisms of skin injury. In particular, we will examine the function of isolated populations of T helper cells and T suppressor/cytotoxic cells and of adherent accessory cells from the patients and from their HLA identical normal siblings in assays of CML, AMLR, IgE synthesis, and cellular proliferation. The relationship of these immunoregulatory abnormalities to mechanisms of skin injury will be examined by: a) assessing the regulation of fibroblast cytotoxic cell activity by T cells; b) defining the target specificity of the fibroblast cytotoxic cell; and c) determining the nature of the mononuclear cell infiltrate in the skin through the use of monoclonal antibodies; and d) studying the effect of circulating cells and of cells recovered from the skin lesions on cultured fibroblast and on mast cells/basophils. Finally, the immunogenetics of A.D. will be studied by examining HLA types and C4 polymorphism. It is hoped that these studies will elucidate some of the underlying immunoregulatory abnormalities in this disease and thus help devise new therapeutic strategies in the treatment of A.D.
