Co-operative action of interleukin-10 and interferon-γ to regulate dendritic cell functions

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Interleukin(IL)-10 and interferon(IFN)-γ double producer is found in a subpopulation of T regulatory type 1 (Tr1) cells and T helper type 1 (Th1). Thus, it is of interest how IL-10 and IFN-γ influence the immune system. However, few studies have addressed the cooperative action of these "immunosuppressive" and "immunostimulatory" cytokines. Here we examined the effect of IL-10 combined with IFN-γ on dendritic cell (DC) functions. Murine bone marrow-derived conventional DCs were stimulated with IL-10 and/or IFN-γ for 24 hr. Tumour necrosis factor (TNF)-α and IL-12 p40 productions by DCs treated with both IL-10 and IFN-γ were significantly lower than those by DCs treated with IL-10 or IFN-γ alone. Major histocompatibility complex class II expression on DCs treated with both cytokines was attenuated compared to that on DCs treated with either cytokine. In contrast, levels of inducible nitric oxide synthase and indoleamine 2,3-dioxygenase, which appear to suppress T-cell responses and promote tolerance, in DCs treated with both cytokines were higher than those in DCs treated with IL-10 or IFN-γ alone. Simultaneous treatment with IL-10 and IFN-γ significantly suppressed ability of DCs to activate CD4+ T cells compared with treatment with either cytokine. Thus, IL-10 and IFN-γ cooperatively suppress the immunostimulatory functions of DCs.
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