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A 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- γ ( IFN- γ) on the differentiation and maturation of human peripheral blood monocyte-derived dendritic cells (mo DC). Here, we report that following differentiation of monocytes into mo DC with granulocyte-macrophage colony-stimulating factor and interleukin-4, IFN- γ induces mo DC maturation and up-regulates the co-stimulatory markers CD80/ CD86/ CD95 and MHC Class I, enabling mo DC 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- γ during differentiation promotes the formation of macrophages. However, under low concentrations of IFN- γ, monocytes continue to differentiate into dendritic cells possessing a unique gene-expression profile, resulting in impairments in subsequent maturation by IFN- γ or lipopolysaccharide and an inability to generate effective antigen-specific CD4+ and CD8+ T-cell responses. These findings demonstrate that IFN- γ imparts differential programmes on mo DC that shape the antigen-specific T-cell responses they induce. Timing and intensity of exposure to IFN- γ can therefore determine the functional capacity of mo DC. [ABSTRACT FROM AUTHOR]