Function Of Plasmacytoid Dendritic Cells In Chronic Hepatitis B With Interferon-α Treatment

Objective: To determine the changes of frequency and function ofcirculating plasmacytoid dendritic cells (pDC) in chronic hepatitis Bpatients at different time point who are undergoing the treatment ofIFN-alpha. To describe the possible mechanism of immune response andantivirus activities associated with pDC, and provide immunological basisfor better use of interferon alpha in treating chronic hepatitis B andformulating a better anti-virus strategy.Materials and methods: Patients using Interferon (conventional orpegylated [PEG]) for the treatment of chronic hepatitis B were enrolled inthe study. All of the patients are positive on HBV surface antigen for at least6-months, HBV e antigen positive, HBV-DNA≥105copies/mL, SerumAlanine aminotransferase (ALT) increased to2-10times the upper limit ofnormal. Patients with other hepatotropic virus infection were excluded.Flow cytometry was used to analyze the frequency and function ofcirculating plasmacytoid dendritic cells at different treatment time (0w,4w,12w,24w),which may provide some evidences for analying factors afecting the role of interferon treatment in chronic hepatitis B patients.Results: The rates of virological response and ALT normalization inchronic hepatitis B received interferon-α therapy after24weeks were70%(21/30) and30%（9/30）,respectively.The frequency of peripheralblood DC and pDC was higher in chronic hepatitis B group than healthycontrols （P <0.05）. The expression of constimulatory molecules CD40,CD80, CD86in plasmacytoid dendritic cells in patients with chronichepatitis B were significantly higher than that of healthy controlgroup（P<0.05）.The expression of these constimulatory molecules inpDC were up-regulated significantly in patients received the therapy ofinterferon.The expression of PD-L1in DC was significantly higher thanhealthy control group, which increased significantly afer undergoinginterferon therapy (P<0.05).The frequency of CD8+T cell was lower inchronic hepatitis B than that of health control.The expression of PD-1onCD4+T and CD8+T cells are significantly higher than that of control group,and no difference were found on PD-1at different time point when receivedinterferon-α therapy.Conclusions: The frequency of DC and pDC in chronic heptitis Bwere higher than that of healthy controls. Interferon treatment couldincrease the frequency of DCs and pDCs.The up-regulation ofconstimulatory molecule s CD40、C D80、 CD86in pDC, indicated thatsustained HBV infection could stimulate the expression of constimulatory molecules,which however, were up-regulated when patients undergoing theinterferon treatment.The up-regulated expression of PD-L1on DC andPD-1on CD4+T and CD8+T cells may associated with impaired ability onstimulating T cell immune response and induced immune tolerance.ThePD-1/PD-L1pathway may be used as new molecular targets for HBVtherapy.