OBJECTIVETo 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.

METHODSDCs 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.

RESULTThe 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.

CONCLUSIONHigh 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.