SummaryA growing body of evidence suggests that inflammatory cytokines have a dualistic role in immunity. In this study, we sought to determine the direct effects of interferon-c (IFN-c) on the differentiation and maturation of human peripheral blood monocyte-derived dendritic cells (moDC). Here, we report that following differentiation of monocytes into moDC with granulocyte-macrophage colony-stimulating factor and interleukin-4, IFN-c induces moDC maturation and up-regulates the co-stimulatory markers CD80/CD86/CD95 and MHC Class I, enabling moDC to effectively generate antigen-specific CD4 + and CD8 + T-cell responses for multiple viral and tumour antigens. Early exposure of monocytes to high concentrations of IFN-c during differentiation promotes the formation of macrophages. However, under low concentrations of IFN-c, monocytes continue to differentiate into dendritic cells possessing a unique geneexpression profile, resulting in impairments in subsequent maturation by IFN-c or lipopolysaccharide and an inability to generate effective antigenspecific CD4 + and CD8 + T-cell responses. These findings demonstrate that IFN-c imparts differential programmes on moDC that shape the antigenspecific T-cell responses they induce. Timing and intensity of exposure to IFN-c can therefore determine the functional capacity of moDC.
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