Immune Regulation in Allergic and Irritant Skin Reactions

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65499/1/j.1365-4362.1991.tb03844.x.pd

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[SUP+] keratinocytes. 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 nonLC 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 antigenpresenting cell activity

Cyclosporine A

Cyclosporine A (CsA) is a neutral lipophilic compound that was first isolated in the 1970s from the fungal species Tolypocladium inflatum gams. CsA is a cyclic polypeptide that consists of 11 amino acids and that has a molecular weight of 1202 daltons.1 It was found to have potent immunosuppressive properties and was initially used in the late 1970s to prevent organ rejection following transplantation. CsA first became available for general use in North America in 1983 and is now perhaps the most widely used drug to prevent graft rejection in transplantation medicine. The spectrum of conditions for which CsA is now being used has broadened, with recent reports of its benefit in several autoimmune and cutaneous diseases.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27861/1/0000274.pd