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The frequency and skewed T-cell receptor beta-chain variable patterns of peripheral CD4+CD25+ regulatory T-cells are associated with hepatitis B e antigen seroconversion of chronic hepatitis B patients during antiviral treatment

Cellular & Molecular Immunology volume 13, pages 678–687 (2016)Cite this article

Abstract

The frequency and T-cell receptor beta-chain variable (TCRBV) patterns of peripheral CD4+CD25+ regulatory T-cells (Tregs) are ambiguously altered in chronic hepatitis B (CHB) patients following tenofovir disoproxil fumarate (TDF) treatment. Moreover, the clinical significance of these parameters in relation to hepatitis B e antigen (HBeAg) seroconversion (SC) is largely unknown. In this study, the circulation of Tregs in HBeAg-positive CHB patients was determined by flow cytometry, and the molecular profiles of frequent TCRBV patterns of Tregs were analyzed using a gene melting spectral pattern. The parameters, such as Treg frequency, the number of skewed TCRBV patterns, hepatitis B virus (HBV) DNA levels, and alanine aminotransferase (ALT) levels, were analyzed by comparing their associations in seroconverting and non-seroconverting patients following TDF treatment. The Treg frequency was significantly correlated with the ALT level in seroconverting but not in non-seroconverting patients. Similarly, skewed TCRBV patterns were remarkably associated with HBV DNA levels in the SC group. Six TCRBV families (BV3, BV11, BV12, BV14, BV20, and BV24) were more prevalent than other TCRBV members in seroconverting patients pretreated with TDF, while BV12, BV15, and BV22 were predominant in non-seroconverting patients during TDF treatment. Taken together, the preferential TCRBV patterns may be associated with immune responses related to SC. The dynamic frequency and skewed TCRBV patterns of peripheral Tregs could contribute to predicting SC in CHB patients. Moreover, the conserved TCRBV complementarity-determining region (CDR3) motif may be targeted to develop personalized immunotherapy for CHB patients.

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Acknowledgements

This study was supported by the Zhejiang province natural science foundation of China (LY15H030008), the National High-technology R&D Program of China (2013CB531406), the National Science and Technology Major Project (2012ZX10002-006), and the Fundamental Research Funds for the Central Universities (2013XZZX010, 2014XZZX008).

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  1. State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, PR China

    Jiezuan Yang, Guoping Sheng, Dangsheng Xiao, Haiyan Shi, Wei Wu, Haifeng Lu, Hongcui Cao & Lanjuan Li

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Yang, J., Sheng, G., Xiao, D. et al. The frequency and skewed T-cell receptor beta-chain variable patterns of peripheral CD4+CD25+ regulatory T-cells are associated with hepatitis B e antigen seroconversion of chronic hepatitis B patients during antiviral treatment. Cell Mol Immunol 13, 678–687 (2016). https://doi.org/10.1038/cmi.2015.100

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