Engagement of human monocyte-derived dendritic cells into interleukin (IL)-12 producers by IL-1β + interferon (IFN)-γ

Dendritic cells (DCs) are potent antigen-presenting cells and can induce tumour- or pathogen-specific T cell responses. For adoptive immunotherapy purposes, immature DCs can be generated from adherent monocytes using granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin (IL)-4, and further maturation is usually achieved by incubation with tumour necrosis factor (TNF)-α. However, TNF-α-stimulated DCs produce low levels of IL-12. In this study, we compared the effects of TNF-α, interferon (IFN)-γ, IL-1β or IFN-γ+ IL-1β on the phenotypic and functional maturation of DCs. Our results show that IFN-γ, but not IL-1β, augmented the surface expression of CD80, CD83 and CD86 molecules without inducing IL-12 production from DCs. However, IL-1β, but not IFN-γ, induced IL-12 p40 production by DCs without enhancing phenotypic maturation. When combined, IFN-γ+IL-1β treatment profoundly up-regulated the expression of CD80, CD83, CD86 and major histocompatibility complex (MHC) class II antigens. Furthermore, IFN-γ+IL-1β-treated DCs produced larger amounts of IL-12 and induced stronger T cell proliferation and IFN-γ secretion in primary allogeneic mixed lymphocyte reaction (MLR) than did TNF-α-treated DCs. Our results show that IFN-γ+IL-1β induced human monocyte-derived DCs to differentiate into Th1-prone mature DCs.