Psoriatic epidermal cells demonstrate increased numbers and function of non-Langerhans antigen-presenting cells

The recent findings that the immunosuppressant cyclosporine A (CsA) improves psoriasis raises the possibility that cellular immune processes play a major role in the pathogenesis of psoriasis. We therefore investigated the phenotype and function of cells within psoriatic epidermis that can play a role in cellular immunologic reactivity. Double fluorescence microscopic studies with monoclonal antibodies of epidermal cells in suspension (EC) and of histologic sections demonstrated that involved psoriatic skin contained a significantly increased number of non-Langerhans cell T6^-DR⁺ EC (4.9 + 2.1%) relative to uninvolved (0.3 ±0.1%), p < 0.01. This non-Langerhans cell population was comprised of DR⁺ monocytes, DR⁺ activated T lymphocytes, a few DR⁺RFD1⁺ antigen-presenting cells (APC), and DR⁺ ke ratinocytes. Langerhans cell (LC) levels in EC suspension were not different between involved and uninvolved psoriatic epidermis. Functional studies demonstrated that involved psoriatic epidermal cells had an increased capacity to induce T-cell activation and proliferation relative to uninvolved EC (p< 0.04). This increased APC activity was due to the non-LC T6^-DR⁺HLe1⁺ APC population and not to DR⁺ keratinocytes. These results demonstrate that involved psoriatic epidermal cells contain both an increased number and function of antigen-presenting cells. The pathogenetic mechanisms in psoriasis may be related to ongoing cellular immune responses in the skin, and the effect of CsA may be mediated through a suppressive effect on the enhanced antigen-presenting cell activity.