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Unpublished Paper
Down-Regulation of PD-1 Expression on Lymphocytes in Chronic Hepatitis B Patients with Pegylated Interferon α-2b Treatment
Journal of Hepatology
  • Ji Chen, Wright State University - Main Campus
  • Y. Wang
  • X. J. Wu
  • G. Q. Wang
Document Type
Conference Proceeding
Publication Date
Background: Programmed death-1(PD-1) represents a mechanism of T cells dysfunction in hepatitis B virus (HBV) persistence. In periphery blood, PD-1 was up-regulated on virus specific-T cells, leading to the impairment of T cells. Aims: To show the effect of pegylated interferon a-2b treatment on the expression of PD-1 on lymphocytes, the frequency of specific T cells, and the correlation with therapeutic effect. Methods: 21 patients with chronic hepatitis B(CHB) were treated by pegylated IFN a-2b (PegIntron from Schering-Plough, once a week, 0.5 or 1 mg/kg/weight). The periphery bloods were taken at 0 weeks, 4 weeks, 8 weeks, 12 weeks, and 24 weeks. Periphery blood mononuclear cells(PBMC) were isolated from fresh heparinized blood by Ficoll-Hypaque(density:1.077g/L) density gradient centrifugation. Expression of PD-1 and frequency of circulating HBV epitope-specific CD8 T cells were detected by flow cytometry(FCM). Cytokines were detected using Cytometric bead assay(CBA). Results: The expression of PD-1 on lymphocytes was decreased consecutive(P < 0.05), and decreases in responders (P = 0.00) were more than non-responders (P > 0.05). Frequency of circulating HBV core or env-specific CD8 T cells was increased in CHB patients after IFN-a-2b therapy(P < 0.05). Furthermore, the elevation of HBV core specific CD8 T cells at 24 weeks were seen in responders, but not non-responders(P < 0.05). However, there were no differences between responders and non-responders in frequency of HBV env specific CD8 T cells. After IFN-a-2b treatment, Th1-type cytokines(IL-12, TNF-a and IFN-g) increased, but Th2-type cytokines(IL-4, IL-6 and IL-10) decreased. IL-6 was correlated with HBV DNA(r = 0.597, P = 0.04), while IP-10 was correlated with serum ALT(r = 0.545, P = 0.005). PD-1 levels at baseline can predict virologic response (PPV = 73%, NPV = 83%). IP-10 levels at 8 weeks can predict ALT normalization (PPV = 56%, NPV = 92%). Conclusions: Treatment with pegylated IFN a-2b can increase the frequency of circulating HBV epitope-specific CD8 T cells, down-regulate the PD-1 expression on lymphocytes. pegylated IFN a-2b can enhance immune response by regulating Th1/Th2 cytokines. This may be one of the mechanism of T cells dysfunction, and monitor the PD-1/PD-L interaction may partially restore the function of T cells.

This paper was presented at the 60th American Association for the Study of Liver Diseases, Boston, MA, 2009.

Citation Information
Ji Chen, Y. Wang, X. J. Wu and G. Q. Wang. "Down-Regulation of PD-1 Expression on Lymphocytes in Chronic Hepatitis B Patients with Pegylated Interferon α-2b Treatment" Journal of Hepatology Vol. 52 (2010) p. S239 - S240 ISSN: 0168-8278
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