Effects of 4-1BB signaling on the biological function of murine dendritic cells.

4-1BB signaling has profound effects on the T cell-induced cell immune response, but its biological function in dendritic cells (DCs) has remained largely uncharacterized. In this study, we investigated the function of 4-1BB in murine DCs with an agonistic mAb to 4-1BB. Interleukin (IL)-6 and IL-12 production was assessed by an enzyme-linked immunosorbent assay (ELISA). Co-stimulatory molecules (CD80 and CD86) in DCs were analyzed by flow cytometry. The results showed that 4-1BB was strongly expressed in DCs during the maturation process. Triggering 4-1BB increased the secretion of IL-6 and IL-12 and the upregulation of co-stimulatory molecules (CD80 and CD86) from DCs, indicating that agonistic mAb to 4-1BB directly improves the activation of DCs. Moreover, triggering 4-1BB induced a higher survival rate of DCs compared to that of hamster IgG isotype control, due to the upregulated expression of Bcl-2 and Bcl-xL. To further assess the role of 4-1BB on DCs stimulating T-cell proliferation, allogeneic mixed lymphocyte reactions were analyzed. The agonistic anti-4-1BB mAb induced a higher T-cell proliferation. These results suggest that 4-1BB affects the duration, DC-T interaction and immunogenicity of DCs.