| Objective: To investigate the features of circulating pDCs in patients with chronic hepatitis B for better understanding the immunopathogenesis of HBV infection. Method: The fresh blood samples were collected from 20 patients with cronic hepatitis B (CHB) and 15 healthy individuals as controls. Liver tissues were obtained from 11 patients with chronic severe hepatitis B and 4 healthy individuals who received liver transplantation. pDCs were isolated from peripheral blood mononuclear cells (PBMCs) using immunomagnetic assay and detected by flow cytometry. Fresh PBMCs and isolated pDCs were stimulated by in vitro CpG ODN2006 or CpG ODN2216 as stimulator, respectively and measured by ELISA for IFN-α production. Result: The frequency of peripheral pDCs in CHB patients was markedly lower than the counterparts in healthy controls. The isolated pDCs pulsed with CpG ODN2216 produced lower levels of IFN- α in the CHB patient group compared with the healthy control group. The CpG ODN2216 drove pDCs to produce more amount of IFN- α than CpG ODN2006, though both are TLR-9 ligands. However the CpG ODN2006 had a stronger capability in up-regulating the express of surface costimulator molecules like CD80, CD86, CD40, CD83 than CpG ODN2116, which is consistent with previous reports. The pDCs frequency in liver infiltrating lymphocytes (LILs) in severe CHB patients was significantly higher than those in healthy controls, which was further confirmed by in situ immunohistochemical staining. Though pDCs frequency of LILs was higher than those in PBMCs in severe CHB patients, however, the LILs generated less amounts of IFN-a compared with the PBMCs under the same stimulation of CpG ODN, suggesting pDCs was, at least in part, dysfunctioned in the liver of severe CHB patients.Conclusions: The reduced numbers and impaired functions of peripheral pDCs may involve in the disease progression in patients with CHB. |
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