肺结核患者外周血T细胞活化亚群和细胞因子的变化
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摘要
目的应用流式细胞术检测结核患者外周血单个核细胞经结核杆菌特异性蛋白刺激前后T细胞表面活化标记以及细胞因子的变化,以探讨其在肺结核发病过程中的意义。方法选择203例结核患者为疾病组,按照痰涂片结果分为涂阳结核组(123例)和涂阴结核组(80例),选择同期的健康人群作为对照组,采用流式细胞技术对其外周血PBMC中的T细胞表面活化标记以及细胞因子进行检测分析。结果结核病组的CD3~+CD25~+、CD4~+CD25~+、CD25~+、CD8~+HLA-DR~+、CD3~+HLA-DR~+、CD8~+CD38~+、CD38~+、CD4~+IFN-γ~+、CD4~+TNF-α~+T细胞的表达与对照组相比显著升高,并且CD4~+TNF-α~+T细胞在涂阳结核组的百分率显著高于涂阴结核组(P<0.05)。结论结核患者体内存在异常活化的淋巴细胞亚群,检测T淋巴细胞表面活化标记及分泌的细胞因子有助于评估结核患者的免疫功能。
Objective Flow cytometry was used to detect the changes of T cell surface activation markers and cytokines in peripheral blood mononuclear cells of tuberculosis patients before and after stimulation with Mycobacterium tuberculosis specific protein, so as to explore its significance in the pathogenesis of tuberculosis. Methods A total of 203 cases of tuberculosis were selected as the case group and divided into smear-positive tuberculosis group(123 cases) and smear-negative tuberculosis group(80 cases) according to the results of sputum smear. In the same period, tuberculosis patients and healthy people were selected as the control group, and flow cytometry was adopted to detect and analyze T cell surface activation markers and cytokines in peripheral blood PBMC. Results Compared to control group, the expressions of CD3~+CD25~+, CD4~+CD25~+, CD25~+, CD8~+HLA-DR~+, CD3~+HLA-DR~+, CD8~+CD38~+, CD38~+, CD4~+IFN-γ~+ and CD4~+TNF-α~+T in the tuberculosis group were significantly higher than that of the control group, and the percentage of CD4~+TNF-α~+T cells in the smear-positive tuberculosis group was significantly higher than that of the smear-negative tuberculosis group(P<0.05). Conclusion Abnormally activated lymphocyte subsets exits in tuberculosis patients, and detection of T lymphocyte surface activation markers and secreted cytokines help to assess the immune function of tuberculosis patients.
Objective Flow cytometry was used to detect the changes of T cell surface activation markers and cytokines in peripheral blood mononuclear cells of tuberculosis patients before and after stimulation with Mycobacterium tuberculosis specific protein, so as to explore its significance in the pathogenesis of tuberculosis. Methods A total of 203 cases of tuberculosis were selected as the case group and divided into smear-positive tuberculosis group(123 cases) and smear-negative tuberculosis group(80 cases) according to the results of sputum smear. In the same period, tuberculosis patients and healthy people were selected as the control group, and flow cytometry was adopted to detect and analyze T cell surface activation markers and cytokines in peripheral blood PBMC. Results Compared to control group, the expressions of CD3~+CD25~+, CD4~+CD25~+, CD25~+, CD8~+HLA-DR~+, CD3~+HLA-DR~+, CD8~+CD38~+, CD38~+, CD4~+IFN-γ~+ and CD4~+TNF-α~+T in the tuberculosis group were significantly higher than that of the control group, and the percentage of CD4~+TNF-α~+T cells in the smear-positive tuberculosis group was significantly higher than that of the smear-negative tuberculosis group(P<0.05). Conclusion Abnormally activated lymphocyte subsets exits in tuberculosis patients, and detection of T lymphocyte surface activation markers and secreted cytokines help to assess the immune function of tuberculosis patients.
引文
[1] 全国第五次结核病流行病学抽样调查技术指导组. 2010年全国第五次结核病流行病学抽样调查报告[J].中国防痨杂志,2012,34(8):485-508.
[2] 中华人民共和国卫生部疾病预防控制局,中华人民共和国卫生部医政司,中国疾病预防控制中心.中国结核病防治规划实施工作指南(2008年版)[M]. 北京:中国协和医科大学出版社,2009.
[3] Kawakami Y. Cancer treatment by comprehensive regulation of anti-tumor immune network[J]. Nihon Rinsho, 2010, 68(6): 1094-1099.
[4] Li Nl, Ji PY, Song LG, et al. The expression of molecule CD28 and CD38 on CD4+/CD8+T lymphocytes in thymus and spleen elicited by Schistosoma japonicum infection in mice model[J]. Parasitol Res, 2015, 24(15): 223-227.
[5] 吴雨洁,李建勇,范磊, 等.分化抗原簇CD38在慢性淋巴细胞白血病T淋巴细胞中的表达研究[J]. 中华检验医学杂志,2008,31(10):1153-1156.
[6] Sullivan ZA, Wong EB, Ndung′u T, et al. Latent and Active Tuberculosis Infection Increase Immune Activation in Individuals Co-Infected with HIV[J]. EBioMedicine, 2015, 2(4): 334-340.
[7] Reiley WW, Shafiani S, Wittmer ST, et al. Distinct functions of antigen specific CD4 T cells during murine Mycobacterium tuberculosis infection[J]. Proc Nat Acad Sci USA, 2010, 107(45): 19408-19413.
[8] Churina EG, Urazova OI, Novitskiy VV, et al. The Role of Foxp3-Expressing Regulatory T Cells and T Helpers in Immunopathogenesis of Multidrug Resistant Pulmonary Tuberculosis[J]. Tuberc Res Treat, 2012, 2012: 931291.
[9] Winslow GM, Cooper A, Reiley W, et al. Early T-cell responses in tuberculosis immunity[J]. Immunol Rev, 2008, 225(1): 284-299.
[10] Dilek F, Ozkaya E, Kocyigit A, et al. Effect of Montelukast Monotherapy on Oxidative Stress Parameters and DNA Damage in Children with Asthma[J]. Int Arch Allergy Immunol, 2015, 167 (2): 119-126.
[11] Green AM, DiFazio R, Flynn JL. IFN-γ from CD4 T cells is essential for host survival and enhances CD8 T cell function during Mycobacterium tuberculosis infection[J]. J Immunol, 2013, 190(1): 270-277.
[12] Cooper AM. Cell-mediated immune responses in tuberculosis[J]. Annu Rev Immunol, 2009, 27: 393-422.
[13] Lasco TM, Yamamoto T, Yoshimura T, et al. Effect of mycobacterium bovis BCG vaccination on mycobacterium-specific cellular proliferation and tumor necrosis factor alpha production from distinct Guinea pig leukocyte populations[J]. Infect Immun, 2003, 71(12): 7035-7042.
[14] Xie X, Li F, Chen JW, et al. Risk of tuberculosis infection in anti-TNF-α biological therapy: from bench to bedside[J]. J Microbiol Immunol Infect, 2014, 47(4): 268-274.
[2] 中华人民共和国卫生部疾病预防控制局,中华人民共和国卫生部医政司,中国疾病预防控制中心.中国结核病防治规划实施工作指南(2008年版)[M]. 北京:中国协和医科大学出版社,2009.
[3] Kawakami Y. Cancer treatment by comprehensive regulation of anti-tumor immune network[J]. Nihon Rinsho, 2010, 68(6): 1094-1099.
[4] Li Nl, Ji PY, Song LG, et al. The expression of molecule CD28 and CD38 on CD4+/CD8+T lymphocytes in thymus and spleen elicited by Schistosoma japonicum infection in mice model[J]. Parasitol Res, 2015, 24(15): 223-227.
[5] 吴雨洁,李建勇,范磊, 等.分化抗原簇CD38在慢性淋巴细胞白血病T淋巴细胞中的表达研究[J]. 中华检验医学杂志,2008,31(10):1153-1156.
[6] Sullivan ZA, Wong EB, Ndung′u T, et al. Latent and Active Tuberculosis Infection Increase Immune Activation in Individuals Co-Infected with HIV[J]. EBioMedicine, 2015, 2(4): 334-340.
[7] Reiley WW, Shafiani S, Wittmer ST, et al. Distinct functions of antigen specific CD4 T cells during murine Mycobacterium tuberculosis infection[J]. Proc Nat Acad Sci USA, 2010, 107(45): 19408-19413.
[8] Churina EG, Urazova OI, Novitskiy VV, et al. The Role of Foxp3-Expressing Regulatory T Cells and T Helpers in Immunopathogenesis of Multidrug Resistant Pulmonary Tuberculosis[J]. Tuberc Res Treat, 2012, 2012: 931291.
[9] Winslow GM, Cooper A, Reiley W, et al. Early T-cell responses in tuberculosis immunity[J]. Immunol Rev, 2008, 225(1): 284-299.
[10] Dilek F, Ozkaya E, Kocyigit A, et al. Effect of Montelukast Monotherapy on Oxidative Stress Parameters and DNA Damage in Children with Asthma[J]. Int Arch Allergy Immunol, 2015, 167 (2): 119-126.
[11] Green AM, DiFazio R, Flynn JL. IFN-γ from CD4 T cells is essential for host survival and enhances CD8 T cell function during Mycobacterium tuberculosis infection[J]. J Immunol, 2013, 190(1): 270-277.
[12] Cooper AM. Cell-mediated immune responses in tuberculosis[J]. Annu Rev Immunol, 2009, 27: 393-422.
[13] Lasco TM, Yamamoto T, Yoshimura T, et al. Effect of mycobacterium bovis BCG vaccination on mycobacterium-specific cellular proliferation and tumor necrosis factor alpha production from distinct Guinea pig leukocyte populations[J]. Infect Immun, 2003, 71(12): 7035-7042.
[14] Xie X, Li F, Chen JW, et al. Risk of tuberculosis infection in anti-TNF-α biological therapy: from bench to bedside[J]. J Microbiol Immunol Infect, 2014, 47(4): 268-274.