Synthetic Retinoids Inhibit the Antigen Presenting Properties of Epidermal Cells in Vitro

The clinical efficacy of retinoids in benign and malignant skin diseases involving immune mechanisms suggests that they affect the immunologic functions of the epidermis. However, these effects have yet to be demonstrated. The action of vitamin A (retinol) and the synthetic retinoids, isotretinoin, etretinate, acitretin, and arotinoid-free acid have been studied on the lymphocyte proliferation induced by phytohemagglutinin (PHA), by the mixed lymphocyte reaction (MLR), and the mixed epidermal cell-lymphocyte reaction (MECLR). The results for PHA-induced proliferations were highly variable for all the retinoids. However, in MECLR the synthetic retinoids consistently reduced the proliferation by 20%–30%. This occurred at therapeutic drug concentrations of about 10-7M. In MLR, a minor decrease of 10%–15% was only found for higher concentrations (10-5M). Retinol induced no effect in either reaction. Further analysis of acitretin on MECLR showed that it reduced lymphocyte proliferation in a dose-dependent fashion. This reduction was combined with a decrease in cytotoxic T-lymphocyte induction (CTL). Addition of 10-6 M acitretin at various times also revealed that its presence at cell culture initiation was necessary to inhibit proliferation significantly. Furthermore, cell treatments prior to MECLR showed that exposure of epidermal cells to acitretin was essential to produce this inhibition, suggesting that it acts directly on epidermal cells. Consequently, it is suggested that the specific inhibitory effect of synthetic retinoids on lymphocyte activation in MECLR may partly account for their therapeutic action on the skin