Objective: To study the effect and mechanism of the dysfunction of CD4+ T cells in the disease process of chronic cardiac failure (CHF).Methods:According to different group technologies, 100 CHF patients were divided ...Objective: To study the effect and mechanism of the dysfunction of CD4+ T cells in the disease process of chronic cardiac failure (CHF).Methods:According to different group technologies, 100 CHF patients were divided into the following groups: ischemia group and non-ischemia group, heart function Ⅰ-Ⅱ group and heart function Ⅲ-Ⅳ group, event group and non-event group, and 50 healthy volunteers were included in the control group. Realtime PCR was used to detect transcription factors T-bet and GATA-3 of Th1 and Th2; flow cytometry was applied to determine the ratio of Th17 and Treg cells; ELISA was employed to test cytokines IFN-γ, IL-4, IL-17 and IL-10 of peripheral blood Th1, Th2, Th17 and Treg cells, respectively; ultrasonic cardiogram was used to exploit to LVEF and LVEDd; and electrochemilu minescene immunoassay was used to examine plasma BNP. The differences of all indexes of all groups were analyzed and the correlation between CD4 T cells and clinical indexes was analyzed by Pearson correlation analysis. Results: As compared to the control group, the transcription factors T-bet and GATA-3 of Th1 and Th2, the ratio of cytokines Th17 and IFN-γ, cytokines IL-17, T-bet/GATA-3, IFN-γ/IL-4, Th17 cells/Treg cells, IL-17/IL-10 of the ischemia group and non-ischemia group, heart functionⅠ-Ⅱgroup and heart function Ⅲ-Ⅳ group, event group and non-event group were all increased significantly, while their transcription factor GATA-3 of Th2, cytokines IL4, Treg cells ratio, cytokines IL10 were decreased obviously. The differences showed statistical significance (P < 0.05). The increase or decrease of the partial CD4+ T cells of the ischemia group, heart function Ⅲ-Ⅳ group and event group was more distinctly. The results of Pearson correlation analysis showed that IFN-γ and IL-17 were significantly positively correlated with LVEDd and BNP, IL-4 and IL-10 were also significantly positively correlated with LVEF, but correlated negatively with BNP, and IL-17 was negatively correlative with LVEF. Concl展开更多
目的探讨生存素(Survivin)调控季节性变应性鼻炎(seasonal allergic rhinitis,SAR)患者鼻黏膜CD4+T细胞凋亡的机制。方法选择2018年5月~2019年5月西安市中医院收治的50例SAR患者为研究组,同期收治的50例单纯进行鼻中隔检查者为对照组,...目的探讨生存素(Survivin)调控季节性变应性鼻炎(seasonal allergic rhinitis,SAR)患者鼻黏膜CD4+T细胞凋亡的机制。方法选择2018年5月~2019年5月西安市中医院收治的50例SAR患者为研究组,同期收治的50例单纯进行鼻中隔检查者为对照组,比较两组鼻黏膜组织中Survivin浓度。分离50例SAR患者鼻黏膜CD4+T细胞,将CD4+T细胞分为空白对照组、阴性对照组、Survivin过表达组,空白对照组不作任何处理,阴性对照组转染无关干扰序列,Survivin过表达组转染Survivin过表达质粒,采用流式细胞术检测各组CD4+T细胞凋亡率,采用Western blot检测各组CD4+T细胞中Survivin、磷脂酰肌醇-3-激酶(phosphoinositide3-kinase,PI-3K)、磷酸化丝氨酸苏氨酸激酶(phosphorylated ser ine threonine kinase,p-AKT)蛋白表达量。结果研究组鼻黏膜组织中Survivin浓度较对照组明显升高(P<0.05);Survivin过表达组CD4+T细胞中Survivin蛋白表达量明显高于空白对照组、阴性对照组(P<0.05);阴性对照组与空白对照组CD4+T细胞中Survivin蛋白表达量比较差异无统计学意义(P>0.05);Survivin过表达组CD4+T细胞凋亡率明显低于空白对照组、阴性对照组(P<0.05);阴性对照组与空白对照组CD4+T细胞凋亡率比较差异无统计学意义(P>0.05);Survivin过表达组CD4+T细胞中PI3K、p-AKT蛋白表达量明显高于空白对照组、阴性对照组(P<0.05);阴性对照组与空白对照组CD4+T细胞中PI3K、p-AKT蛋白表达量比较差异无统计学意义(P>0.05)。结论Survivin可能通过激活PI3K/AKT信号通路抑制SAR患者鼻黏膜CD4+T细胞凋亡。展开更多
Neonates are at increased risk of viral encephalopathies that can result in neurological dysfunction, seizures, permanent disability and even death. The neurological damage results from the combined effect of the viru...Neonates are at increased risk of viral encephalopathies that can result in neurological dysfunction, seizures, permanent disability and even death. The neurological damage results from the combined effect of the virus and the immune response it elicits, thus finding tools to facilitate viral clearance from central nervous system （CNS） while minimizing neuron damage remains a critical challenge. Neonatal mice inoculated intraperitoneally with Tacaribe virus （TCRV） develop seizures, hindlimb paralysis and death within 15 days of inoculation. TCRV localizes to the CNS within days of challenge, primarily infecting astrocytes in the cerebellum and brain stem. We show that infection leads to inflammation, T cell and monocyte infiltration into the cerebellar parenchyma, apoptosis of astrocytes, neuronal degeneration and loss of Purkinje cells. Infiltrating antigen-specific T cells fail to clear the virus but drive the disease, as T-cell-deficient CD3ε KO mice survive TCRV infection with minimal inflammation or clinical manifestations despite no difference in CNS viral loads in comparison with T-cell sufficient mice. CD8＋ T cells drive the pathology, which even in the absence of CD4＋ T-cell help, infiltrate the parenchyma and mediate the apoptotic loss of cerebellar astrocytes, neurodegeneration and loss of Purkinje cells resulting in loss of balance, paralysis and death. CD4＋ T cells are also pathogenic inducing gliosis and inflammation in the cerebellum and cerebrum that are associated with wasting and death several weeks after CD4＋ T-cell transfer. These data demonstrate distinct pathogenic effects of CD4＋ and CD8＋ T cells and identify them as possible therapeutic targets.展开更多
Context: The functional activity of NK cells depends on the balance between the engagement of activating and inhibitory receptors on the cell surface with their ligands, which enables them to kill infected cells. Obje...Context: The functional activity of NK cells depends on the balance between the engagement of activating and inhibitory receptors on the cell surface with their ligands, which enables them to kill infected cells. Objectives: The aim of this study was to evaluate and compare expressions of selected activating and inhibitory receptors on stimulated NK cells in HIV-1 and HIV-2 infections. Methods: PBMCs were analysed for activating (NKp30, NKp44, NKp46) and inhibitory (CD158a, CD158b, p70) receptor expressions in 30 HIV-1, 30 HIV-2 and 30 HIV uninfected healthy control (HC) subjects by flow cytometry after stimulating with K562 cells. Results: There was an expression of other receptors following an already in vitro engagement of NK cells with K562 cells. Higher expression of the activating receptors, NKp44 (p = 0.029) and NKp46 (p = 0.032) on NK cells from HIV-2 compared to HIV-1 infected individuals but similar NKp30 expression (p = 0.980). The levels of expression of inhibitory receptor CD158a were similar between HIV-1 and HIV-2 infected subjects (p = 0.309) but there was significant up-regulation of inhibitory receptors p70 (p = 0.010) and CD158b (p = 0.05) in HIV-1 compared to HIV-2 subjects. Conclusion: Despite the in vitro engagement of NK cells with stimulating K562 cells, our data showed differential expressions of other selected activating and inhibitory receptors in HIV-1 and HIV-2 infected subjects.展开更多
Context: Human Natural Killer T cells are T lymphocytes that express an invariant αβ T cells receptors and NK cells receptors. They regulate innate and adaptive immune response but are susceptible to HIV-1 infection...Context: Human Natural Killer T cells are T lymphocytes that express an invariant αβ T cells receptors and NK cells receptors. They regulate innate and adaptive immune response but are susceptible to HIV-1 infection. Objective: We compare the frequency and the activity of NKT cells in HIV-1 and HIV-2 infected individuals with CD4+ counts greater than 500/mm3 using flow cytometry after overnight stimulation with phytohemagglutinin (PHA). Results: The frequency of NKT cells was similar between both groups and also to sero-negative control subjects. There were also no significant differences in the proportions of total NKT cells and the CD4+ NKT subset that secreted interferon gamma (IFN-γ) after polyclonal stimulation. However, there was a significantly higher frequency of IFN-γ﹣ CD4+ NKT cells in HIV-1-infected compared with HIV-2 infected subjects (p = 0.043). Conclusion: These data suggest there is no relationship between the functional activity of NKT cell subsets and the total NKT cell population in HIV infection. The expansion of IFN-γ﹣ CD4+ NKT cells in HIV-1 infection may serve as target for viral infection and may eventually result in their depletion during chronic infection.展开更多
基金supported by the Brainstorm Project of Guizhou Science and Technology Office (Grant No.SY 20133016)Guiyang Science and Technology Planning Project (Grand No.20151001)
文摘Objective: To study the effect and mechanism of the dysfunction of CD4+ T cells in the disease process of chronic cardiac failure (CHF).Methods:According to different group technologies, 100 CHF patients were divided into the following groups: ischemia group and non-ischemia group, heart function Ⅰ-Ⅱ group and heart function Ⅲ-Ⅳ group, event group and non-event group, and 50 healthy volunteers were included in the control group. Realtime PCR was used to detect transcription factors T-bet and GATA-3 of Th1 and Th2; flow cytometry was applied to determine the ratio of Th17 and Treg cells; ELISA was employed to test cytokines IFN-γ, IL-4, IL-17 and IL-10 of peripheral blood Th1, Th2, Th17 and Treg cells, respectively; ultrasonic cardiogram was used to exploit to LVEF and LVEDd; and electrochemilu minescene immunoassay was used to examine plasma BNP. The differences of all indexes of all groups were analyzed and the correlation between CD4 T cells and clinical indexes was analyzed by Pearson correlation analysis. Results: As compared to the control group, the transcription factors T-bet and GATA-3 of Th1 and Th2, the ratio of cytokines Th17 and IFN-γ, cytokines IL-17, T-bet/GATA-3, IFN-γ/IL-4, Th17 cells/Treg cells, IL-17/IL-10 of the ischemia group and non-ischemia group, heart functionⅠ-Ⅱgroup and heart function Ⅲ-Ⅳ group, event group and non-event group were all increased significantly, while their transcription factor GATA-3 of Th2, cytokines IL4, Treg cells ratio, cytokines IL10 were decreased obviously. The differences showed statistical significance (P < 0.05). The increase or decrease of the partial CD4+ T cells of the ischemia group, heart function Ⅲ-Ⅳ group and event group was more distinctly. The results of Pearson correlation analysis showed that IFN-γ and IL-17 were significantly positively correlated with LVEDd and BNP, IL-4 and IL-10 were also significantly positively correlated with LVEF, but correlated negatively with BNP, and IL-17 was negatively correlative with LVEF. Concl
文摘目的探讨生存素(Survivin)调控季节性变应性鼻炎(seasonal allergic rhinitis,SAR)患者鼻黏膜CD4+T细胞凋亡的机制。方法选择2018年5月~2019年5月西安市中医院收治的50例SAR患者为研究组,同期收治的50例单纯进行鼻中隔检查者为对照组,比较两组鼻黏膜组织中Survivin浓度。分离50例SAR患者鼻黏膜CD4+T细胞,将CD4+T细胞分为空白对照组、阴性对照组、Survivin过表达组,空白对照组不作任何处理,阴性对照组转染无关干扰序列,Survivin过表达组转染Survivin过表达质粒,采用流式细胞术检测各组CD4+T细胞凋亡率,采用Western blot检测各组CD4+T细胞中Survivin、磷脂酰肌醇-3-激酶(phosphoinositide3-kinase,PI-3K)、磷酸化丝氨酸苏氨酸激酶(phosphorylated ser ine threonine kinase,p-AKT)蛋白表达量。结果研究组鼻黏膜组织中Survivin浓度较对照组明显升高(P<0.05);Survivin过表达组CD4+T细胞中Survivin蛋白表达量明显高于空白对照组、阴性对照组(P<0.05);阴性对照组与空白对照组CD4+T细胞中Survivin蛋白表达量比较差异无统计学意义(P>0.05);Survivin过表达组CD4+T细胞凋亡率明显低于空白对照组、阴性对照组(P<0.05);阴性对照组与空白对照组CD4+T细胞凋亡率比较差异无统计学意义(P>0.05);Survivin过表达组CD4+T细胞中PI3K、p-AKT蛋白表达量明显高于空白对照组、阴性对照组(P<0.05);阴性对照组与空白对照组CD4+T细胞中PI3K、p-AKT蛋白表达量比较差异无统计学意义(P>0.05)。结论Survivin可能通过激活PI3K/AKT信号通路抑制SAR患者鼻黏膜CD4+T细胞凋亡。
文摘Neonates are at increased risk of viral encephalopathies that can result in neurological dysfunction, seizures, permanent disability and even death. The neurological damage results from the combined effect of the virus and the immune response it elicits, thus finding tools to facilitate viral clearance from central nervous system （CNS） while minimizing neuron damage remains a critical challenge. Neonatal mice inoculated intraperitoneally with Tacaribe virus （TCRV） develop seizures, hindlimb paralysis and death within 15 days of inoculation. TCRV localizes to the CNS within days of challenge, primarily infecting astrocytes in the cerebellum and brain stem. We show that infection leads to inflammation, T cell and monocyte infiltration into the cerebellar parenchyma, apoptosis of astrocytes, neuronal degeneration and loss of Purkinje cells. Infiltrating antigen-specific T cells fail to clear the virus but drive the disease, as T-cell-deficient CD3ε KO mice survive TCRV infection with minimal inflammation or clinical manifestations despite no difference in CNS viral loads in comparison with T-cell sufficient mice. CD8＋ T cells drive the pathology, which even in the absence of CD4＋ T-cell help, infiltrate the parenchyma and mediate the apoptotic loss of cerebellar astrocytes, neurodegeneration and loss of Purkinje cells resulting in loss of balance, paralysis and death. CD4＋ T cells are also pathogenic inducing gliosis and inflammation in the cerebellum and cerebrum that are associated with wasting and death several weeks after CD4＋ T-cell transfer. These data demonstrate distinct pathogenic effects of CD4＋ and CD8＋ T cells and identify them as possible therapeutic targets.
文摘Context: The functional activity of NK cells depends on the balance between the engagement of activating and inhibitory receptors on the cell surface with their ligands, which enables them to kill infected cells. Objectives: The aim of this study was to evaluate and compare expressions of selected activating and inhibitory receptors on stimulated NK cells in HIV-1 and HIV-2 infections. Methods: PBMCs were analysed for activating (NKp30, NKp44, NKp46) and inhibitory (CD158a, CD158b, p70) receptor expressions in 30 HIV-1, 30 HIV-2 and 30 HIV uninfected healthy control (HC) subjects by flow cytometry after stimulating with K562 cells. Results: There was an expression of other receptors following an already in vitro engagement of NK cells with K562 cells. Higher expression of the activating receptors, NKp44 (p = 0.029) and NKp46 (p = 0.032) on NK cells from HIV-2 compared to HIV-1 infected individuals but similar NKp30 expression (p = 0.980). The levels of expression of inhibitory receptor CD158a were similar between HIV-1 and HIV-2 infected subjects (p = 0.309) but there was significant up-regulation of inhibitory receptors p70 (p = 0.010) and CD158b (p = 0.05) in HIV-1 compared to HIV-2 subjects. Conclusion: Despite the in vitro engagement of NK cells with stimulating K562 cells, our data showed differential expressions of other selected activating and inhibitory receptors in HIV-1 and HIV-2 infected subjects.
文摘Context: Human Natural Killer T cells are T lymphocytes that express an invariant αβ T cells receptors and NK cells receptors. They regulate innate and adaptive immune response but are susceptible to HIV-1 infection. Objective: We compare the frequency and the activity of NKT cells in HIV-1 and HIV-2 infected individuals with CD4+ counts greater than 500/mm3 using flow cytometry after overnight stimulation with phytohemagglutinin (PHA). Results: The frequency of NKT cells was similar between both groups and also to sero-negative control subjects. There were also no significant differences in the proportions of total NKT cells and the CD4+ NKT subset that secreted interferon gamma (IFN-γ) after polyclonal stimulation. However, there was a significantly higher frequency of IFN-γ﹣ CD4+ NKT cells in HIV-1-infected compared with HIV-2 infected subjects (p = 0.043). Conclusion: These data suggest there is no relationship between the functional activity of NKT cell subsets and the total NKT cell population in HIV infection. The expansion of IFN-γ﹣ CD4+ NKT cells in HIV-1 infection may serve as target for viral infection and may eventually result in their depletion during chronic infection.
