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Immune response pattern varies with the natural history of chronic hepatitis B

World Journal of Gastroenterology 2019年第16期25卷 1950-1963页

作者： Wen-Tao Wang Xue-Qi Zhao Gui-Ping Li Yi-Zhi Chen Lin Wang Mei-Fang Han Wei-Na Li Tao Chen Guang Chen Dong Xu Qin Ning Xi-Ping Zhao Department of Infectious Diseases Tongji Hospital Tongji Medical CollegeHuazhong University of Science and Technology Huazhong University of Science and Technology Department of Heart Function Examination Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Department of Pathophysiology Hubei University of Medicine

BACKGROUND Chronic hepatitis B is a highly heterogeneous disease that can be divided into four phases: Immune tolerant(IT), immune active(IA), inactive carrier(IC) and hepatitis B envelope antigen(HBeAg)-negative hepatitis(ENEG).AIM To investigate the immune status of natural killer(NK) and T cells in different phases of chronic hepatitis *** The frequency, phenotype and function of circulating NK cells, as well as nonantigen-specific and hepatitis B virus(HBV)-specific T cell responses were detected by flow cytometry in healthy and HBV-infected *** The ability of NK cells to produce IFN-γ was markedly attenuated in HBVinfected patients overall but was less compromised in IC patients. Patients in the IT and IA phases also displayed significantly lower TNF-α production compared to healthy subjects. NK cells were phenotypically activated in the IA and ENEGphases, as evidenced by the upregulation of NKp44 in CD56^(bright) NK cells and CD69 in CD56^(dim) NK cells. Furthermore, global T-cells from the ENEG phase displayed a proinflammatory cytokine profile with upregulated IFN-γ and TNF-αexpression, while this profile was suppressed in IT and IA patients. Finally, core and S antigen-specific T cell responses were significantly stronger after in vitro expansion in the IC phase compared to other *** Our findings demonstrate the changes in immune response pattern during the natural history of HBV infection. Both NK and T cells are functionally impaired in the IT and IA phases. With the spontaneous clearance of HBeAg and hepatitis B surface antigen decline, NK cell cytokine production and HBV-specific T responses are partially restored in IC phase, and the ENEG phase is dominated by nonantigen-specific T cell responses.

关键词： Chronic hepatitis Hepatitis B virus Natural killer cells Global-T cells virusspecific T cells Natural history Heterogeneity

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