Wang Xinjing, Meng Xianghong, Zheng Yue, Jiang Jing, Yang Bingfen, Liu Yanhua, Zhai Fei, Cheng Xiaoxing
Key Laboratory of Tuberculosis Prevention and Treatment of PLA, Division of Research, Institute of Tuberculosis, 309 Hospital, Beijing, China.
Key Laboratory of Tuberculosis Prevention and Treatment of PLA, Division of Research, Institute of Tuberculosis, 309 Hospital, Beijing, China; Chinese Academy of Military Medical Sciences, Beijing, China.
Tuberculosis (Edinb). 2014 Sep;94(5):469-74. doi: 10.1016/j.tube.2014.03.009. Epub 2014 May 14.
The functional role of ILT2 in anti-tuberculosis immunity remains to be elucidated. In this study, we investigated expression and functions of ILT2 on NK cells during TB infection. The frequency of CD56(dim)CD16(+) NK cells that expressed ILT2 was significantly elevated in patients with active pulmonary TB as compared with tuberculin-positive healthy controls (p < 0.0001). TB patients with Mycobacterium tuberculosis smear/culture-positive result had significantly higher frequency of ILT2-expressing CD56(dim)CD16(+) NK cells than those with M. tuberculosis smear/culture-negative result (p < 0.0001), suggesting that ILT2 expression on CD56(dim)CD16(+) NK cells correlated with disease severity of pulmonary TB. ILT2-expressing CD56(dim) NK cells had a functional defect, as evidenced by reduced expression of CD107a and IFN-γ. Spontaneous apoptosis in ILT2(+)CD56(dim) NK cells was higher than in ILT2(-) cells. Blocking of ILT2 signaling resulted in increased expression of CD107a on CD56(dim)CD16(+) NK cells. It is concluded that ILT2 has an inhibitory role on NK cells in patients with active TB.
ILT2在抗结核免疫中的功能作用仍有待阐明。在本研究中,我们调查了结核感染期间NK细胞上ILT2的表达及功能。与结核菌素阳性的健康对照相比,活动性肺结核患者中表达ILT2的CD56(dim)CD16(+) NK细胞频率显著升高(p < 0.0001)。结核分枝杆菌涂片/培养结果为阳性的肺结核患者中,表达ILT2的CD56(dim)CD16(+) NK细胞频率显著高于涂片/培养结果为阴性的患者(p < 0.0001),这表明CD56(dim)CD16(+) NK细胞上的ILT2表达与肺结核的疾病严重程度相关。表达ILT2的CD56(dim) NK细胞存在功能缺陷,CD107a和IFN-γ表达降低证明了这一点。ILT2(+)CD56(dim) NK细胞的自发凋亡高于ILT2(-)细胞。阻断ILT2信号传导导致CD56(dim)CD16(+) NK细胞上CD107a表达增加。得出的结论是,ILT2对活动性肺结核患者的NK细胞具有抑制作用。