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

Interleukin-10 (IL-10) and interferon-gamma (IFN-gamma) double producer is found in a subpopulation of T regulatory type 1 (Tr1) and T helper type 1 (Th1) cells. Consequently, it is of interest how IL-10 and IFN-gamma influence the immune system. However, few studies have addressed the co-operative action of these 'immunosuppressive' and 'immunostimulatory' cytokines. Here, we examine the effect of IL-10 combined with IFN-gamma on dendritic cell (DC) functions. Murine bone marrow-derived conventional DCs were stimulated with IL-10 and/or IFN-gamma for 24 hr. Tumour necrosis factor-alpha and IL-12 p40 production by DCs treated with both IL-10 and IFN-gamma was significantly lower than that by DCs treated with IL-10 or IFN-gamma alone. Major histocompatibility complex class II expression on DCs treated with both cytokines was attenuated compared with that on DCs treated with either cytokine alone. 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-gamma alone. Simultaneous treatment with IL-10 and IFN-gamma significantly suppressed the ability of DCs to activate CD4+ T cells compared with treatment with either cytokine. Therefore, IL-10 and IFN-gamma co-operatively suppress the immunostimulatory functions of DCs.