Potent T cell stimulatory material with antigenic properties in stratum corneum of normal human skin

Abstract

T cell mediated autoimmunity may be important in inflammatory skin disease, but target autoantigens have not previously been described. In studies aimed at defining T cell epitopes, aqueous extracts of normal facial and plantar stratum corneum have consistently been found to induce potent proliferation of peripheral blood mononuclear cells from normal donors and patients with inflammatory skin disease, giving stimulation indices up to 80. Potent stimulation was seen with both autologous and allogeneic stratum corneum extracts. Because of the presence of inhibitory material, demonstration of the stimulatory activity was critically dependent on extract concentration, and was facilitated by short-term pulsing of cultures with extract. The proliferation of cells purified from peripheral blood mononuclear cells by immunomagnetic beads and immunophenotyping of cell lines generated from peripheral blood mononuclear cells, confirmed the T cell nature of the response to stratum corneum extracts. The activity was inhibited by HLA-DR monoclonal antibody, indicating the presence of antigen or super-antigen. Tetanus toxoid reactive clones and a purified protein derivative reactive line failed to respond to the stratum corneum extracts, indicating that the active material is not a nonspecific T cell stimulant such as a cytokine or mitogen. This and the failure of recombinant interleukin-1α to stimulate peripheral blood mononuclear cells in concentrations up to 1000 U per ml, indicate that the activity is not due to interleukin-1. We propose the hypothesis that antigenic or super-antigenic material is normally sequestered from the immune system in the epidermis, but induces T cell activation when released following wounding and in disease, and that this represents an important and previously unrecognized pathogenic mechanism.