Effects of T cell immunoglobulin and mucin domain-containing molecule-3 signaling molecule on human monocyte-derived dendritic cells with hepatitis B virus surface antigen stimulation in vitro.

The aim of the present study was to investigate the in vitro effects of hepatitis B virus surface antigen (HBsAg) on the immune function of human monocyte-derived dendritic cells (MD-DCs), and the moderating role of T cell immunoglobulin and mucin domain-containing molecule-3 (Tim-3) signaling molecule. The monocytes, obtained from healthy adult peripheral blood, were incubated with recombinant human granulocyte-macrophage colony-stimulating factor and interleukin (IL)-4 to induce DCs. DC-associated cell markers were detected using flow cytometry. MD-DCs were treated with HBsAg (5 μg/ml) in vitro for 48 h and subsequently, cell markers, lymphocyte stimulatory capacity, signaling protein and downstream cytokines were assessed. In addition, a Tim-3 monoclonal antibody was used to inhibit the Tim-3 signaling pathway, and subsequently the immune responses of MD-DCs to HBsAg stimulation were determined using the aforementioned method. The cell phenotype expressions of MD-DCs were all significantly increased with cluster of differentiation (CD)11c at 70.09±0.57%, human leukocyte antigen-DR at 79.83±2.12%, CD80 at 48.33±7.34% and CD86 at 44.21±5.35%. The treatment of MD-DCs with HBsAg resulted in a CD80 and CD86 enhanced expression, enhanced lymphocyte stimulatory capacity, upregulated expression of Tim-3 and nuclear factor-κB (NF-κB), as well as enhanced cytokine secretion of IL-6, IL-10 and interferon (IFN)-γ. However, a reduced immune response of MD-DCs in response to HBsAg stimulation was observed when the Tim-3 signaling pathway was inhibited prior to stimulation. The expression of NF-κB was decreased and the cytokine secretion level of IL-6, IL-10 and IFN-γ were downregulated. The treatment with HBsAg in vitro resulted in an enhanced immune response of MD-DCs, which may be positively regulated by the Tim-3 signaling molecule. [ABSTRACT FROM AUTHOR]