IL-12 promotes the accessory cell function of epidermal Langerhans cells

The objective of this study was to investigate the effects of cytokines regulating cutaneous immune responses, on the accessory cell function of epidermal cells (EC). EC were treated with various cytokines, and the accessory cell function of the cytokine-pretreated EC was examined by the allogeneic mixed epidermal cell-lymphocyte reaction (MECLR). Among the cytokines examined, IFN-gamma- and IL-12-pretreated EC augmented IFN-gamma production in the MECLR, while none of the other cytokines was effective. However, the cytokine-pretreated EC did neither affect T cell proliferation nor IL-4 production in the MECLR. Next we attempted to analyze the mechanisms by which IL-12-pretreated EC increase IFN-gamma production in the MECLR. Endogenous IFN-gamma produced during the IL-12 pretreatment of EC was found to play only a minor role in modulating the function of EC. The expression of MHC class II, CD80 and CD86 on EC was not affected by IL-12. On the other hand, soluble mediators that induce IFN-gamma production during the MECLR containing IL-12-pretreated EC were identified as endogenously produced IL-12 (the major mediator) and IL-18 (the minor mediator). Furthermore, the results of depletion experiments indicate that IL-12 promotes the accessory cell function of Langerhans cells to responder T cells in inducing IFN-gamma production in the MECLR.