Institute of Immunology, Zhongshan School of Medicine, Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou, Guangdong, China Chest Hospital of Guangzhou, Guangzhou, China.
Scand J Immunol. 2011 Apr;73(4):330-7. doi: 10.1111/j.1365-3083.2011.02512.x.
Th1 cell-mediated adaptive immune response is very important but may not be sufficient to control Mycobacterium tuberculosis (M. tuberculosis) infection. The roles of the various T cell subsets and cytokines in the inflammatory processes are not clearly elucidated. We investigated whether Th1, Th22 and Th17 cells mediated cellular immunity at the local site of M. tuberculosis infection in patients with tuberculous pleurisy (TBP). The results showed that the cytokines IFN-γ and IL-22 but not IL-17 were elevated in tubercular pleural fluid. Following stimulation with immune-dominant peptides of early secreted antigenic target-6 (ESAT-6), culture filtrate protein-10 (CFP-10) or Bacille Calmette-Guerin, pleural fluid mononuclear cells expressed high levels of cytokines IFN-γ, IL-22 and IL-17 as revealed by mRNA and protein measurements. In addition, we showed that cytokines IFN-γ, IL-22 and IL-17 were produced in M. tuberculosis-specific immune response by distinct subsets of CD4+ T cells with the phenotype of CD45RA-CD62L-CCR7+CD27+ . Our results demonstrated for the first time that ESAT-6- and CFP-10-specific Th1, Th22 and Th17 cells existed in the patients with TBP and might play an essential role against M. tuberculosis infection. The findings of this study raised the possibility of unravelling the critical targets for therapeutic intervention in chronic inflammatory diseases such as TBP.
Th1 细胞介导的适应性免疫反应非常重要,但可能不足以控制结核分枝杆菌(M. tuberculosis)感染。各种 T 细胞亚群和细胞因子在炎症过程中的作用尚未明确阐明。我们研究了结核性胸膜炎(TBP)患者结核分枝杆菌感染局部部位的 Th1、Th22 和 Th17 细胞是否介导细胞免疫。结果表明,结核性胸腔积液中 IFN-γ 和 IL-22 但不是 IL-17 升高。在用早期分泌抗原靶-6(ESAT-6)、培养滤液蛋白-10(CFP-10)或卡介苗的免疫优势肽刺激后,胸腔液单个核细胞通过 mRNA 和蛋白测量显示高水平表达细胞因子 IFN-γ、IL-22 和 IL-17。此外,我们表明,通过 CD45RA-CD62L-CCR7+CD27+表型的 CD4+T 细胞的不同亚群产生了针对 M. tuberculosis 的 IFN-γ、IL-22 和 IL-17 特异性免疫反应中的细胞因子。我们的研究结果首次表明,TBP 患者中存在 ESAT-6 和 CFP-10 特异性 Th1、Th22 和 Th17 细胞,它们可能在对抗结核分枝杆菌感染中发挥重要作用。这项研究的结果提出了一种可能性,即可以揭示慢性炎症性疾病(如 TBP)治疗干预的关键靶标。