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学科主题传染病学
HIV(+)潜在及活动型结核杆菌感染者结核杆菌特异性CD4+T淋巴细胞分泌IFN-γ与TNF-α状况研究
刘娟
2014-04-28
导师伦文辉
专业传染病学
授予单位北京大学
授予地点北京地坛医院教学医院
学位硕士
关键词HIV 结核杆菌 CD4+T淋巴细胞 IFN-γ TNF-α 活动 潜在
其他题名Comparation of IFN-γ and TNF-α secretion in Mycobacterium tuberculosis-specific CD4+ T lymphocytes between HIV-1 infected individuals with latent tuberculosis infection and active tuberculosis
分类号R512.91
摘要目的 对比分析HIV(+)潜在结核患者及活动性结核患者结核杆菌特异性CD4+T淋巴细胞分泌IFN-γ与TNF-α的情况,探讨在HIV感染状态下结核杆菌特异性CD4+T淋巴细胞的功能状态,进一步探索HIV感染者结核杆菌潜在感染及活化状态CD4+T淋巴细胞免疫反应状态差异,探讨HIV感染者结核病发病机制。方法 (1)运用ELISPOT-IFN-γ方法检测受试者的结核杆菌特异性T淋巴细胞反应,根据其结核杆菌特异性T淋巴细胞反应强度判断其是否为结核杆菌感染者。(2)运用流式细胞术研究结核杆菌特异性T淋巴细胞分泌IFN-γ与TNF-α的功能。结果 (1)ESAT6-CFP10刺激后,四组的CD4+T淋巴细胞表达IFN-γ和TNF-α均显著增加(P<0.05)。HIV(+)aTB(+)组CD8+T淋巴细胞表达IFN-γ增加(P<0.05),其余三组CD8+T淋巴细胞表达IFN-γ无显著差异。(2)HIV(+)aTB(+)组IFN-γ+CD4+T淋巴细胞百分比高于HIV(+)LTB(+)组(Z=-3.563, P=0.000)。HIV(+)aTB(+)组TNF-α+CD4+T淋巴细胞百分比高于HIV(+)LTB(+)组(Z =-3.509, P=0.000)。HIV(-)aTB(+)组IFN-γ+CD4+T淋巴细胞百分比低于HIV(-)LTB(+)组(Z=-2.225, P =0.026)。HIV(-)aTB(+)组TNF-α+CD4+T淋巴细胞百分比高于HIV(-)LTB(+)组,差异不具有统计学意义(Z =-0.79, P =0.43)。HIV(+)aTB(+)组IFN-γ+CD4+T淋巴细胞百分比高于HIV(-)aTB(+)组(Z =-4.174, P=0.000)。HIV(+)aTB(+)组TNF-α+CD4+T淋巴细胞百分比高于HIV(-)aTB(+)组(Z =-3.349, P =0.001)。HIV(+)LTB(+)组与HIV(-)LTB(+)组IFN-γ+CD4+T淋巴细胞百分比、TNF-α+CD4+T淋巴细胞百分比均无显著性差异。(3)HIV(+)aTB(+)组IFN-γ+TNF-α- CD4+T淋巴细胞百分比高于HIV(+)LTB(+)组,差异具有统计学意义(Z=-3.375, P=0.001),IFN-γ+TNF-α+ CD4+T淋巴细胞群的百分比高于HIV(+)LTB(+)组,差异具有统计学意义(Z=-3.645, P=0.000)。HIV(-)aTB(+)组IFN-γ+TNF-α- ESAT6-CFP10特异性CD4+T淋巴细胞群的百分比低于HIV(-)LTB(+)组,差异具有统计学意义(Z=-2.289, P=0.022),IFN-γ-TNF-α+ CD4+ T淋巴细胞群的百分比高于HIV(+)LTB(+)组,差异具有统计学意义(Z=-2.122, P=0.034)。 HIV(+)aTB(+)组IFN-γ+TNF-α- CD4+T淋巴细胞群的百分比高于HIV(-)aTB(+)组,差异具有统计学意义(Z=-4.224, P=0.000),IFN-γ+TNF-α+ CD4+T淋巴细胞群的百分比高于HIV(-)aTB(+)组,差异具有统计学意义(Z=-4.102, P=0.000)。HIV(+)LTB(+)组与HIV(-)LTB(+)组无显著差异。结论(1)ESAT6-CFP10刺激后,四组的CD4+T淋巴细胞表达IFN-γ和TNF-α均显著增加。HIV(+)活动性结核组CD8+T淋巴细胞表达IFN-γ增加,其余三组CD8+T淋巴细胞表达IFN-γ无显著差异,表明结核杆菌感染者外周血单个核细胞产生IFN-γ的细胞主要为CD4+T淋巴细胞。(2)HIV(+)活动性结核者结核杆菌特异性CD4+T淋巴细胞表达IFN-γ、TNF-α水平高于HIV(+)潜在结核感染者。(3)HIV(+)活动性结核感染组IFN-γ+TNF-α-结核杆菌特异性CD4+T淋巴细胞百分比与IFN-γ+TNF-α+结核杆菌特异性CD4+T淋巴细胞百分比显著高于HIV(+)潜在结核感染组。HIV感染者结核杆菌潜在感染状态与活化状态下结核杆菌特异性CD4+T淋巴细胞免疫反应状态存在差异。
英文摘要Objective To analysis the secretion of IFN-γ and TNF-α in Mycobacterium tuberculosis-specific CD4+ T lymphocytes in HIV infected persons between latent tuberculosis infection and active tuberculosis. To investigate the functional status of mycobacterium tuberculosis-specific CD4+ T lymphocytes under HIV infected status, and further explore the differences of immune response of CD4+ T lymphocytes between latent tuberculosis infection and activated status in HIV-infected persons. To investigate the pathogenesis of tuberculosis in HIV infected persons. Methods (1) ELISPOT-IFN-γ was used to detecte the response of MTB specific T lymphocytes of the subjects, and then according to the intensity of response to determine whether the subjects had been infected by Mycobacterium tuberculosis. (2) Flow cytometry was used to study the function of MTB-specific T lymphocytes to secrete IFN-γ and TNF-α. Results (1) The expression of IFN-γ and TNF-α in CD4+T lymphocytes were significantly increased in the four groups after ESAT6-CFP10 stimulation (P<0.05). The expression of IFN-γ in CD8+ T lymphocytes increased in the HIV (+) aTB (+) group (P<0.05).There were no significant differences in the remaining three groups. (2) The percentage of IFN-γ+CD4+ T lymphocytes in HIV (+) aTB (+) group was higher than HIV (+) LTB (+) group (Z=-3.563, P=0.000). The percentage of TNF-α+ CD4+ T lymphocytes in HIV (+) aTB (+) group was higher than HIV(+) LTB (+) group (Z=-3.509, P=0.000). The percentage of IFN-γ+CD4+ T lymphocytes in HIV (-) aTB (+) group was higher than HIV (-) LTB (+) group (Z=-2.225, P=0.026). The percentage of TNF-α+ CD4+ T lymphocytes in HIV (-) aTB (+) group was higher than HIV (-) LTB (+) group, the difference was not statistically significant (Z=-0.79, P=0.43). The percentage of IFN-γ+CD4+ T lymphocytes in HIV (+) aTB (+) group was higher than HIV (-) aTB (+) group (Z=-4.174, P=0.000). The percentage of TNF-α+ CD4+ T lymphocytes in HIV (+) aTB(+) group was higher than HIV (-) aTB (+) group (Z=-3.349, P=0.001). There were no significant difference between the HIV(+) LTB (+) group and the HIV (-) LTB (+) group on the percentage of IFN-γ+CD4+ T lymphocytes and TNF-α+CD4+ T lymphocytes. (3) The percentage of IFN-γ+TNF-α-CD4+ T lymphocytes in HIV (+) aTB (+) group was higher than HIV (+) LTB (+) group, the difference was statistically significant (Z=-3.375, P=0.001).The percentage of IFN-γ+TNF-α+CD4+ T lymphocytes in HIV (+) aTB (+) group was higher than HIV (+) LTB (+) group, the difference was statistically significant (Z=-3.645, P=0.000). The percentage of IFN-γ+TNF-α-CD4+ T lymphocytes in HIV (-) aTB (+) group was lower than HIV (-) LTB (+) group, the difference was statistically significant (Z=-2.289, P=0.022).The percentage IFN-γ-TNF-α+CD4+ T lymphocytes in HIV (-) aTB (+) group was higer than HIV (-) LTB (+) group, the difference was statistically significant (Z=-2.122, P=0.034). The percentage of IFN-γ+TNF-α-CD4+ T lymphocytes in HIV (+) aTB (+) group was higher than HIV (-) aTB (+) group, the difference was statistically significant (Z=-4.224, P=0.000). The percentage of IFN-γ+TNF-α+CD4+ T lymphocytes was higher than HIV (-) aTB (+) group, the difference was statistically significant (Z=-4.102, P=0.000). There were no statistically differences between HIV (+) LTB (+) group and HIV (-) LTB (+) group. Conclusions (1) The expression of IFN-γ and TNF-α in CD4+ T lymphocytes were significantly increased in the four groups after ESAT6-CFP10 stimulation. The expression of IFN-γ in CD8+ T lymphocytes increased in HIV (+) aTB (+) group and there were no significant difference in the expression of IFN-γ in CD8+ T lymphocytes in the remaining three groups, which indicated that the cells which produce IFN-γ were mainly CD4+ T lymphocytes in peripheral blood mononuclear cells of TB-infected persons. (2) The expression of IFN-γ and TNF-α by Mycobacterium tuberculosis-specific CD4+ T lymphocytes in HIV(+) persons with active tuberculosis was higher than HIV(+) persons with latent tuberculosis infection and HIV(-) persons with active tuberculosis. (3) The percentage of IFN-γ+TNF-α-MTB-specific CD4+T lymphocytes and the percentage of IFN-γ+TNF-α+MTB-specific CD4+T lymphocytes in HIV(+) persons with active tuberculosis group were significantly higher than HIV(+) with latent tuberculosis group. There were differences in the immune response of Mycobacterium tuberculosis-specific CD4+T lymphocytes between latent tuberculosis infection state and activation state in HIV-infected persons.
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条目标识符http://ir.bjmu.edu.cn/handle/400002259/107984
专题北京地坛医院教学医院
作者单位北京地坛医院教学医院
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刘娟. HIV(+)潜在及活动型结核杆菌感染者结核杆菌特异性CD4+T淋巴细胞分泌IFN-γ与TNF-α状况研究[D]. 北京地坛医院教学医院. 北京大学,2014.
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