IL-17 and IFN-γ expression in lymphocytes from patients with active tuberculosis correlates with the severity of the disease
IL-17 and IFN-γ expression in lymphocytes from patients with active tuberculosis correlates with the severity of the disease
复制标题
DOI：
10.1189/jlb.1211619
复制
发表时间：
2012-06-01
影响因子：
5.5
通讯作者：
Garcia, Veronica E.
中科院分区：
文献类型：
--
作者：
Jurado, Javier O.;Pasquinelli, Virginia;Garcia, Veronica E.
Th1淋巴细胞在抗结核分枝杆菌免疫反应中起着至关重要的作用。然而，仅有干扰素-γ是不足以完全根除细菌的，这表明可能需要其他细胞因子来清除病原体。Th17细胞与结核分枝杆菌感染有关，但产生IL-17的细胞在人类结核病中的作用仍有待了解。因此，我们研究了干扰素-γ和IL-17在疾病活动过程中的诱导和调节。根据T细胞对结核分枝杆菌抗原的应答，将患者分为高反应者和低应答者，观察结核分枝杆菌刺激后胸腔积液和外周血中细胞因子的表达。然后，分析细胞因子产生细胞比例与临床参数之间的潜在相关性。在结核病患者中，结核分枝杆菌产生了干扰素-γ和IL-17，但与卡介苗接种的健康献血员相比，干扰素-γ水平显著降低，而IL-17水平显著升高。此外，IL-17的主要来源是由干扰素-γ调节的Th1/Th17亚群中的CD4(+)IFN-+γIL-17(+)淋巴细胞。有趣的是，结核病患者外周血和胸水中抗原扩增的CD4(+)-干扰素-+-γ-IL-17(+)淋巴细胞的比率与与疾病严重程度相关的临床参数直接相关。的确，低应答率结核病患者中检测到的CD4(+)干扰素-+干扰素-+IL-17(+)细胞比例最高，他们表现出严重的肺部损害，疾病进展时间最长。本研究结果提示，分析肺结核患者外周血中CD4(+)-干扰素-+-γ-IL-17(+)T淋巴细胞的增殖状态可作为判断活动性肺结核临床转归的指标。J.Leukoc。比奥尔。91：991-1002；2012。
Th1 lymphocytes are crucial in the immune response against Mycobacterium tuberculosis. Nevertheless, IFN-gamma alone is not sufficient in the complete eradication of the bacteria, suggesting that other cytokines might be required for pathogen removal. Th17 cells have been associated with M. tuberculosis infection, but the role of IL-17-producing cells in human TB remains to be understood. Therefore, we investigated the induction and regulation of IFN-gamma and IL-17 during the active disease. TB patients were classified as High and Low Responder individuals according to their T cell responses against the antigen, and cytokine expression upon M. tuberculosis stimulation was investigated in peripheral blood and pleural fluid. Afterwards, the potential correlation among the proportions of cytokine-producing cells and clinical parameters was analyzed. In TB patients, M. tuberculosis induced IFN-gamma and IL-17, but in comparison with BCG-vaccinated healthy donors, IFN-gamma results were reduced significantly, and IL-17 was markedly augmented. Moreover, the main source of IL-17 was represented by CD4(+)IFN-+gamma IL-17(+) lymphocytes, a Th1/Th17 subset regulated by IFN-gamma. Interestingly, the ratio of antigen-expanded CD4(+)IFN-+gamma IL-17(+) lymphocytes, in peripheral blood and pleural fluid from TB patients, was correlated directly with clinical parameters associated with disease severity. Indeed, the highest proportion of CD4(+)IFN-+gamma IL-17(+) cells was detected in Low Responder TB patients, individuals displaying severe pulmonary lesions, and longest length of disease evolution. Taken together, the present findings suggest that analysis of the expansion of CD4(+)IFN-+gamma IL-17(+) T lymphocytes in peripheral blood of TB patients might be used as an indicator of the clinical outcome in active TB. J. Leukoc. Biol. 91: 991-1002; 2012.