Combinations of IFN-γ and IL-4 induce distinct profiles of dendritic cell-associated immunoregulatory properties

Interferon gamma (IFN-γ) and interleukin-4 (IL-4) are not only generated during cell-mediated immunity (CMI) and humoral immunity (HI), but are also generated by innate immune cells in response to pathogenic factors. How these cytokines differentially effect the development of dendritic cell (DC)-associated immunoregulatory properties from progenitor cells during innate immunity is unresolved. To address this we have utilized a homogeneous DC progenitor-like cell line, MTHO-D2, as a model to examine cytokine-induced maturation of DCs. By 6 h IFN-γ induced genes that are important for antiviral activity and development of CMI, whereas IL-4 induced genes involved in cellular adhesion, uptake of extracellular antigen, suppression of cytotoxic T-cell responses, and that repair the extracellular matrix. By 48 h the cytokine stimulus had induced many properties characteristic of immature DCs; however, these were differentially effected by IFN-γ and IL-4. IFN-γ induced the greatest levels of costimulatory/activation marker expression, and the highest levels of T-cell proliferation, whereas IL-4 induced the greatest levels of phagopytic activity. Stimulation of the cells with CD40 Ab enhanced the levels of costimulatory marker expression and T-cell stimulatory capacity of cells exposed to IFN-γ, but had little effect on cells exposed to IL-4 in the absence of IFN-γ.