☆ 4.5 Article

Correlation between low tapasin expression and impaired CD8+ T-cell function in patients with chronic hepatitis B

MOLECULAR MEDICINE REPORTS (2016)

Journal

MOLECULAR MEDICINE REPORTS

Volume 14, Issue 4, Pages 3315-3322

Publisher

SPANDIDOS PUBL LTD

DOI: 10.3892/mmr.2016.5610

Keywords

chronic hepatitis B; cytotoxic T lymphocyte; tapasin; adaptive immune response

Funding

Education Committee of Scientific Research Innovation Foundation of Shanghai [1522013]

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Abstract

Recent studies have demonstrated that chronic hepatitis B virus (HBV) infection is associated with reduced antigen-presenting capacity and insufficient cytotoxic T lymphocyte (CTL) production. The molecular chaperone tapasin mediates binding of the transporter associated with antigen processing (TAP), and has an important role in endogenous antigen processing and presentation, and the induction of specific CTL responses. The present study aimed to determine whether tapasin is associated with chronic HBV (CHB) infection. The mRNA expression levels of tapasin were detected in peripheral blood mononuclear cells from 27 patients with CHB, 20 patients with acute HBV (AHB) and 26 healthy controls by reverse transcription-quantitative polymerase chain reaction. In addition, CD8(+) T immune responses were evaluated in all groups, and the correlation between tapasin expression and CD8(+) responses was analyzed. The results demonstrated that the mRNA expression levels of tapasin were significantly downregulated in patients with CHB compared with in healthy controls and patients with AHB. Furthermore, the apoptotic rate of CD8(+) T cells was increased in patients with CHB compared with in the other two groups. The percentage of interferon (IFN)-(+)CD8(+) T cells was reduced in patients with CHB compared with in patients with AHB and healthy controls, and serum cytokine levels (IFN-, interleukin-2 and tumor necrosis factor-) were generally low in patients with CHB. Furthermore, the mRNA expression levels of tapasin were positively correlated with IFN- production by CD8(+) T cells, and were inversely correlated with the apoptotic ratio of CD8(+) T cells. These results indicate that decreased expression of tapasin may be closely associated with CHB, and suggest an important role for tapasin in the pathogenesis of CHB.

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Assessing the chronic hepatitis B adaptive immune response by profiling specific T-cell receptor repertoire

Xueying Li, Anqi Zheng, Jiabang Liu, Mengfen Shi, Baolin Liao, Shi Xie, Rong Yan, Yifan Gan, Xuan Zuo, Mingxing Gong, Hongkai Wu, Zhanhui Wang

Summary: Challenges still exist in assessing HBV-specific T cell immunity in chronic hepatitis B patients, including the need for large quantities of cells. In this study, a dataset of HBV-specific T cell receptor beta chains (TCR beta s) was established using public databases and samples from acute hepatitis B patients. Analysis of the potential HBV-specific TCR beta s from chronic hepatitis B patients showed that individuals with better therapy response may rely more on newly emerging TCR beta s. Furthermore, the characteristics of potential HBV-specific clusters were found to differ between chronic hepatitis B and hepatocellular carcinoma patients in a cross-sectional study. Our strategy provides a convenient method for assessing HBV-specific T cell immunity using a small blood sample.

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