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Updated: May 21, 2026
Development and Functional Characterization of Murine Tolerogenic Dendritic Cells
Published on: May 18, 2018
Effects of 4-1BB signaling on the biological function of murine dendritic cells
Youlin Kuang1, Xiaodong Weng, Xiuheng Liu
1Department of Urology, Renmin Hospital of Wuhan University, Wuhan 430060, P.R. China.
Insights
This study reveals that 4-1BB signaling enhances dendritic cell (DC) activation and survival. Targeting 4-1BB in DCs boosts T-cell proliferation, improving DC-T cell interactions and immune response.
Area of Science:
- Immunology
- Cell Biology
Background:
- The role of 4-1BB signaling in dendritic cells (DCs) is not well understood.
- 4-1BB is known to impact T cell-mediated immune responses.
Purpose of the Study:
- To investigate the function of 4-1BB in murine dendritic cells.
- To determine if 4-1BB activation influences DC maturation, cytokine production, and T-cell stimulation.
Main Methods:
- Used an agonistic monoclonal antibody (mAb) to 4-1BB in murine DCs.
- Assessed IL-6 and IL-12 production via ELISA.
- Analyzed co-stimulatory molecules (CD80, CD86) using flow cytometry.
- Evaluated DC survival by examining Bcl-2 and Bcl-xL expression.
- Measured T-cell proliferation in allogeneic mixed lymphocyte reactions.
Main Results:
- 4-1BB expression is upregulated on DCs during maturation.
- Activating 4-1BB increased IL-6 and IL-12 secretion and CD80/CD86 expression in DCs.
- 4-1BB activation enhanced DC survival by upregulating Bcl-2 and Bcl-xL.
- Agonistic anti-4-1BB mAb treatment led to increased T-cell proliferation.
Conclusions:
- 4-1BB directly enhances dendritic cell activation and survival.
- Targeting 4-1BB in DCs improves their ability to stimulate T-cell proliferation.
- 4-1BB signaling modulates DC-T cell interactions and overall immunogenicity.
Abstract:
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.
