Interferon-gamma production by human cord blood monocyte-derived dendritic cells

Interferon (IFN)-γ is produced by T cells and natural killer cells and activates monocytes and dendritic cells (DCs). Recently, IFN-γ has been shown to be produced by mouse DCs following stimulation with interleukin (IL)-12, which is markedly augmented by the addition of IL-18. We here analyzed whether human DCs secrete IFN-γ in response to IL-12 and/or IL-18. Human immature DCs, generated from cord blood CD14⁺ monocytes by treating with granulocyte–macrophage colony-stimulating factor and IL-4, were incubated with IL-12 and/or IL-18 and assayed for IFN-γ production. IL-12, but not IL-18, weakly induced IFN-γ production, while IL-12 together with IL-18 induced high levels of IFN-γ production. Similar results were obtained with mature DCs, although levels of IFN-γ production were less than those in immature DCs. Also with mature and immature DCs, IL-12 upregulated the expression of IL-18 receptor α (Rα), and costimulation with IL-12 and IL-18 upregulated CD40 expression. Anti-IL-18Rα antibody abrogated both the IFN-γ induction and the CD40 upregulation by IL-12 plus IL-18. These findings suggest that IL-12 upregulates IL-18Rα expression on human DCs and acts synergistically with IL-18 to induce high levels of IFN-γ, which subsequently enhances CD40 expression on DCs in an autocrine manner.