Key Laboratory of Tuberculosis Prevention and Treatment, Division of Research, Institute of Tuberculosis, 309th Hospital, Beijing, China.
Am J Respir Crit Care Med. 2014 Aug 1;190(3):329-39. doi: 10.1164/rccm.201401-0106OC.
Mucosal-associated invariant T (MAIT) cells have been proven to play an important role in host defense against mycobacterial infection in animal infection models; however, the functional role of MAIT cells in patients with active tuberculosis (TB) is still largely unknown.
To understand the clinical features and functions of MAIT cells in patients with active TB.
MAIT cells were analyzed in patients with pulmonary TB, tuberculous pleurisy, and tuberculous peritonitis by flow cytometry. The functions of MAIT cells were compared between patients with active TB and healthy control subjects.
The frequency of MAIT cells was significantly reduced both in peripheral blood from patients with active pulmonary TB (P < 0.0001) and in tuberculous pleural effusions compared with healthy control subjects but not in ascitic fluids from patients with tuberculous peritonitis. A comparison of bacillus Calmette-Guérin (BCG)-stimulated cytokine production showed that patients with active TB had significantly higher production of IFN-γ (P = 0.0034) and tumor necrosis factor (TNF)-α (P = 0.0399) compared with healthy control subjects. In contrast, when MAIT cells were stimulated with Escherichia coli, patients with active TB had significantly lower production of IFN-γ (P = 0.0007) and TNF-α (P = 0.0032). MAIT cells in patients with active TB exhibited elevated expression of programmed death-1 (PD-1) (P = 0.0015), and blockade of PD-1 signaling resulted in a significantly higher frequency of BCG-stimulated IFN-γ production in MAIT cells (P = 0.0178).
MAIT-cell immune response to antigen stimulation in patients with active TB is regulated by PD-1, which could be a potential target for TB immunotherapy.
黏膜相关恒定 T（MAIT）细胞已被证明在动物感染模型中对抗分枝杆菌感染的宿主防御中发挥重要作用；然而，MAIT 细胞在活动性肺结核（TB）患者中的功能作用在很大程度上仍不清楚。
了解活动性 TB 患者 MAIT 细胞的临床特征和功能。
通过流式细胞术分析肺结核、结核性胸膜炎和结核性腹膜炎患者的 MAIT 细胞。比较活动性 TB 患者与健康对照者 MAIT 细胞的功能。
与健康对照者相比，活动性肺结核患者外周血（P<0.0001）和结核性胸腔积液中 MAIT 细胞的频率均显著降低，但结核性腹膜炎患者的腹水则无此现象。比较卡介苗（BCG）刺激细胞因子产生的结果显示，与健康对照者相比，活动性 TB 患者 IFN-γ（P=0.0034）和 TNF-α（P=0.0399）的产生明显更高。相比之下，当用大肠埃希菌刺激 MAIT 细胞时，活动性 TB 患者 IFN-γ（P=0.0007）和 TNF-α（P=0.0032）的产生明显更低。活动性 TB 患者的 MAIT 细胞表达程序性死亡-1（PD-1）明显增加（P=0.0015），阻断 PD-1 信号会导致 MAIT 细胞中 BCG 刺激 IFN-γ产生的频率显著增加（P=0.0178）。
在活动性 TB 患者中，抗原刺激 MAIT 细胞的免疫反应受 PD-1 调节，这可能是 TB 免疫治疗的一个潜在靶点。
