Characterization And Biological Significance Of Circulating Dendritic Cell Subsets In Chronically HBV-infected Children With Interferon-α Treatment

Much progress has been made in the field of dendritic cells (DCs) in host immunity, but the role of DC subsets during the chronic Hepatitis B virus (HBV) infection in humans is less well characterized than the role of cellular immune response like CD8 T cells. In particular, the changes of DC property in HBV patients who are undergoing IFN-alpha treatment have not been reported before. To address these issues, this study was attempted to characterize circulating and intrahepatic DC subsets and their responses to IFN-α therapy in pediatric HBV-infected children in comparison with their counterpart in uninfected healthy children.Thirty pediatric patients with chronic HBV infection including sixteen HBV carriers and twenty-five healthy individuals as controls were enrolled in our study. We characterize circulating and intrahepatic DC subset counts and function by flow cytometry, ELISA assay and immunohistochemical staining in these children. On the other hand, we longitudinally studied circulating DC levels and serum Th1 cytokine production in aforementioned HBV carriers undergoing IFN-a treatment. Our results indicate that circulating myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs) are numerically decreased and subsequently produce less IFN-a in chronic HBV-infected children versus children carries HBV or normal donors. The accumulation of intrahepatic DC subsets was observed in pediatric patients, which may contribute to the reduction of circulating DCs in chronic HBV-infected children. Circulating pDC counts were significantly positively correlated with serum HBV DNA levels in asymptomatic HBV carriers ( r=0.5464, P =0.0351). And mDC counts were significantly negatively correlated with serum HBV DNA levels in chronicHBV-infected children( r =-0.4554, P =0.0194). More importantly, we found that responders who had HBeAg seroconversion and sustained viral response to IFN-a therapy exhibited a peak levels of pDC counts and IFN-a production at median 12th week after initially rapid decrease of within 2 weeks of antiviral treatment, showing a reverse "V" type. The pDC peak, simultaneously accompanying with the loss of plasma HBV viral load and HBeAg seroconversion, followed by the increases of circulating mDC level and serum Thl cytokine production.Our novel findings showed that DC subset recover, in particular for pDC numerical and functional recovery correlated with full viral suppression and ALT normalization in complete responders, suggesting that the recovery of DC subsets probably are an important indicator for the outcome of patients with IFN-alpha antiviral treatment in children. These findings will help us to get an interesting insight into the immune pathogenesis of chronic HBV infection in vivo as well as to design a more reasonable, yet highly effective immune therapeutic regimen, most likely combined with antiviral drug treatment, for chronic HBV patients.