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 hepa...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 B.METHODS 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 subjects.RESULTS 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 phases.CONCLUSION 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.展开更多
To explore the role of bcl-2 and bax genes in the apoptosis of human U937 cells induced by E.coli, flow cytometry assay with annexinⅤ-FITC/PI double staining was used to determine the condition of apoptosis, and the ...To explore the role of bcl-2 and bax genes in the apoptosis of human U937 cells induced by E.coli, flow cytometry assay with annexinⅤ-FITC/PI double staining was used to determine the condition of apoptosis, and the expressions of mRNA of bcl-2 and bax genes were assayed with RT-PCR. It was found that the apoptosis of human U937 cells could be induced by E.coli at various concentration ratios between cells and bacteria for 30 min in a dose-dependent manner. The apoptotic rates at cell/bacteria ratios of 0, 1∶5, 1∶10, 1∶20, 1∶50 and 1∶100 were 3.16%±0.90%, 9.46%±0.84%, 17.90%±1.41%, 35.59%±3.76%, 38.35%±7.12% and 55.07%±5.82% respectively. Also, there was a tendency of alterations in the expression levels of bcl-2 and bax genes with an increased expression level of bax gene and a reduced expression level of bcl-2 gene. It is concluded that E.coli can induce apoptosis in human U937 cells with a down-regulated expression of Bcl-2 and an up-regulated expression of Bax, and this might be related to the induction of apoptosis of the infected cell.展开更多
基金Supported by National Science Fund of China(NSFC)No.30771911National Science and Technology Major Project No.2012ZX10002007-003
文摘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 B.METHODS 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 subjects.RESULTS 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 phases.CONCLUSION 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.
文摘To explore the role of bcl-2 and bax genes in the apoptosis of human U937 cells induced by E.coli, flow cytometry assay with annexinⅤ-FITC/PI double staining was used to determine the condition of apoptosis, and the expressions of mRNA of bcl-2 and bax genes were assayed with RT-PCR. It was found that the apoptosis of human U937 cells could be induced by E.coli at various concentration ratios between cells and bacteria for 30 min in a dose-dependent manner. The apoptotic rates at cell/bacteria ratios of 0, 1∶5, 1∶10, 1∶20, 1∶50 and 1∶100 were 3.16%±0.90%, 9.46%±0.84%, 17.90%±1.41%, 35.59%±3.76%, 38.35%±7.12% and 55.07%±5.82% respectively. Also, there was a tendency of alterations in the expression levels of bcl-2 and bax genes with an increased expression level of bax gene and a reduced expression level of bcl-2 gene. It is concluded that E.coli can induce apoptosis in human U937 cells with a down-regulated expression of Bcl-2 and an up-regulated expression of Bax, and this might be related to the induction of apoptosis of the infected cell.
