DEVELOPMENTAL REGULATION BY CYTOKINES OF BONE-MARROW-DERIVED DENDRITIC CELLS AND EPIDERMAL LANGERHANS CELLS

Dendritic cells (DC) are specialized antigen-presenting cells involved in T cell-mediated immune responses, Differentiation and functional m aturation of the DC are now known to be regulated by various cytokines , including TGF-beta 1. The experiments of this study examined the eff ect of other cytokines, such as IL-4, IL-10 and IL-6, on the different iation and maturation of bone marrow (BM)-derived DC (BM-DC) and epide rmal Langerhans cells (LC), When IL-6 or IL-10 was added to cultures o f BM cells in the presence of GM-CSF, both cytokines, as in the case o f TGF-beta 1, suppressed the maturation of DC in terms of the expressi on of adhesion and costimulatory molecules and T cell-stimulating acti vity. In contrast, IL-4 was not suppressive but rather supportive for the differentiation of DC, However, these suppressive cytokines hardly counteracted the maturation-inducing activity of TNF-alpha when added to cultures of immature DC, In addition, they appeared to block the o vermaturation of DC, which is characterized by a loss of MHC class II molecules, Regarding LC maturation in epidermal cell cultures, IL-6 an d IL-10 were inhibitory for the expression of CD86 and CD80 in a dose- dependent fashion. Unlike BM-DC, LC maturation was slightly enhanced b y TGF-beta 1, The protein antigen-presentation by LC to Th1 clone was not affected by IL-6, but slightly reduced by IL-10, These results sug gest that each cytokine contributes to regulate the differentiation an d maturation of DC at a different developmental stage.