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Open Access Research

Pegylated interferon α enhances recovery of memory T cells in e antigen positive chronic hepatitis B patients

Yong Zhe Liu1, Feng Qin Hou1, Peng Ding23, Yuan Yuan Ren1, Shi Hong Li1 and Gui Qiang Wang1*

Author Affiliations

1 Department of Infectious Diseases and Research Center for Liver Diseases, Peking University First Hospital, Beijing, 100034, People’s Republic of China

2 Institution of Public Health Inspection in Ningxia Hui Autonomous Region, Ningxia Hui Autonomous Region, 750004, People’s Republic of China

3 College of Public Health, Hebei United University, Hebei province, 063000, People's Republic of China

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Virology Journal 2012, 9:274  doi:10.1186/1743-422X-9-274

Published: 16 November 2012

Abstract

Background

Interferons (IFNs) are a group of cytokines commonly used in the clinical treatment of chronic hepatitis B (CHB) patients. Their therapeutic effects are highly correlated with recovery of host antiviral immunity. Clearance of hepatitis B virus (HBV) is mediated partially by activated functional memory T cells. The aims of the present study were to investigate memory T cell status in patients with different outcomes following pegylated interferon-α (IFN-α) therapy and to identify new biomarkers for predicting antiviral immune responses.

Methods

Peripheral blood cells were isolated from 23 CHB patients who were treated with pegylated IFN-α at week 0 (baseline) and week 24. Co-expression of programmed death-1 (PD-1) and CD244 in CD45RO positive T cells, as well as a subset of CD127 and CXCR4 positive memory T cells were assessed. In addition, perforin, granzyme B, and interferon-γ (IFN-γ) expressions were also analyzed by flow cytometric analysis after intracytoplasmic cytokine staining (ICCS). Peripheral blood mononuclear cells (PBMC) isolated at week 24 were re-challenged with exogenous HBV core antigen, and the percentage of IFN-γ expression, serum HBV DNA loads, and ALT (alanine aminotransferase) levels were evaluated.

Results

At week 24, PD-1 and CD244 expression in CD8 memory T cells were down-regulated (P < 0.05, P < 0.05, respectively), along with decreased HBV DNA loads (P < 0.05), while the expressions of partial effector molecules in CD8 and CD4 memory T cells was up-regulated (P < 0.05,P < 0.05, respectively), especially in the responders. CD127 and CXCR4 were highly expressed in CD8 memory T cells after pegylated IFN-α treatment (P < 0.05), which was inversely correlated with HBV DNA loads (r = −0.47, P = 0.001). The responders had a higher IFN-γ expression in memory T cells than the non-responders did after HBV antigen re-stimulation in vitro.

Conclusion

Pegylated IFN-α treatment enhanced recovery of memory T cells in CHB patients by down-regulating inhibitory receptors and up-regulating effector molecules. The expressions of CXCR4 and CD127 in CD8 memory T cell may be used as biomarkers for predicting the outcome of treatment.

Keywords:
Chronic hepatitis B; Pegylated interferon-α therapy; Memory T cell; Intracytoplasmic cytokine staining (ICCS)