Cell-mediated cytotoxicity against skin fibroblasts in atopic dermatitis.

Abstract

The cytotoxicity of peripheral blood mononuclear cells (PBMC) against 51Chromium- (51Cr) labeled cultured autologous skin fibroblasts were determined in three groups of subjects: 12 patients with atopic dermatitis (A.D.). six patients with other diffuse skin diseases, and eight healthy subjects. The mean percent 51Cr release in the patients with A.D. (24.0%) was significantly higher (p < 0.01) than in the patients with other diffuse skin diseases (6.8%) and in the healthy subjects (9.2%). Increased cytotoxic activity of A.D. mononuclear cells (against allogeneic fibroblasts from normal or A.D. subjects) rather than increased susceptibility of the A.D. fibroblasts to lysis accounted for the autocytotoxicity in most of the patients with A.D. The cytotoxic cell was nonadherent to plastic surfaces and did not bear surface immunoglobulins. Its action was independent of serum factors. Cytotoxicity against fibroblasts was detected in both the E rosette-forming and the non-E rosette-forming cell fractions and was inhibited by aggregated human IgG. Complement-dependent lysis of PBMC from A.D. patients with monoclonal antibodies to T11 (reactive with the sheep red cell receptor on T cells) or to M1 (reactive with circulating monocytes and NK cells) resulted in marked reduction of fibroblast cytotoxicity. In contrast, treatment of A.D. PBMC with monoclonal antibodies to T3, a T cell antigen, and complement enriched for fibroblast cytotoxic activity. The enhanced cytotoxic activity against skin fibroblasts observed in patients with A.D. was not associated with increased natural killer (NK) cell activity against 51Cr-labeled K562 targets.The present data indicate that patients with A.D. have circulating NK-like cells cytotoxic to autologous skin fibroblasts, raising the possibility that cell-mediated mechanisms can play a role in the pathogenesis of skin disease.