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Published on: February 19, 2019
[PD-L1 expression in circulating dendritic cells of patients with chronic hepatitis B]
Guo-ping Peng1, Wen Sun, Wei Wu
1Institute of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China.
Insights
In chronic hepatitis B (CHB) patients, PD-L1 expression on dendritic cells (DCs) is elevated and linked to viral load. Blocking PD-L1 with an antibody enhances DC function, suggesting a role in T cell exhaustion.
Area of Science:
- Immunology
- Hepatology
- Virology
Context:
- Chronic hepatitis B (CHB) is a persistent viral infection.
- Immune evasion is a hallmark of CHB.
- Dendritic cells (DCs) play a crucial role in initiating immune responses.
Purpose:
- To quantify Programmed Death-Ligand 1 (PD-L1) expression on circulating DCs in HBeAg-positive CHB patients.
- To assess the impact of anti-PD-L1 antibody on DC-mediated allogeneic lymphocyte stimulation.
Summary:
- PD-L1, but not PD-L2, was significantly upregulated on circulating DCs in CHB patients compared to resolved hepatitis B and healthy controls.
- Higher PD-L1 expression correlated positively with serum HBV DNA viral load.
- DCs from CHB patients exhibited reduced capacity to stimulate allogeneic T cell proliferation, which was restored by PD-L1 blockade in vitro.
Impact:
- Elevated PD-L1 on DCs may contribute to T cell exhaustion in CHB.
- Targeting the PD-L1 pathway could be a therapeutic strategy for CHB.
- Understanding DC dysfunction in CHB offers insights into immune persistence.
Objective:
To determine the PD-L1 expression levels in circulating dendritic cells(DCs) of patients with HBeAg positive chronic hepatitis B, and to investigate the effects of anti-PD-L1 antibody on DCs stimulating capacity of allogeneic lymphocytes.
Methods:
DCs were separated and induced from 22 HBeAg positive chronic hepatitis B patients (CHB), 8 acute resolved hepatitis B patients (AHB) and 10 healthy blood donors. PD-L1 and PD-L2 expression in DCs were determined using real-time RT-PCR and flow cytometry. The potential of circulating DCs on the proliferation of allogeneic T cells was detected and a specific monoclonal antibody against PD-L1 was used in alternative experiments. Serum HBV-DNA titers were measured using real-time PCR, and HBV markers and liver function were also evaluated.
Result:
The expression of PD-L1 but not PD-L2 was upregulated in circulating DCs of CHB patients, compared to AHB patients and healthy controls (both P<0.01). CHB patients with greater than 106 copies /ml of serum HBV DNA loads had a higher level of PD-L1 in circulating DCs than those with less than 106 copies/ml (P<0.05), and the high expression of PD-L1 in DCs was positively correlated with the plasma viral load. Moreover, the potential of circulating DCs from CHB patients was significantly decreased compared with healthy controls or AHB patients, while the blockade of PD-L1 using anti-PD-L1 monoclonal antibody increased the ability of DCs on the proliferation of allogeneic T cells in vitro.
Conclusion:
High expression of PD-L1 on circulating DCs may be associated with T cell exhaustion and persistent high levels of HBV DNA replication in chronic hepatitis B patients.
