The Affiliation Infections Diseases Hospital, Suzhou Medical College of Soochow University, SuZhou, China.
Department of Clinical Laboratory, The Fifth People's Hospital of Suzhou, Suzhou, China.
Microb Pathog. 2023 Jun;179:106089. doi: 10.1016/j.micpath.2023.106089. Epub 2023 Mar 31.
Lymphocyte-activation gene 3 (LAG-3) plays an important role in regulating T-cell responses and inducing peripheral tolerance. Our aim in this study was to investigate the relationship between LAG-3 and active tuberculosis (ATB) and the impact of LAG-3 blockade on CD8T cells.
Flow cytometry was used to detect the expression of LAG-3 on CD4T and CD8T cells in the peripheral blood and bronchoalveolar lavage fluid from ATB patients and to explore the relationship between LAG-3 and ATB.
The expression of LAG-3 on CD4T and CD8T cells in ATB patients was increased (P < 0.001), and CD8T cells with high expression of LAG-3 were associated with sputum culture results (P < 0.05). We further analyzed the relationship between the expression of LAG-3 in CD8T cells and the severity of tuberculosis and found that the expression of LAG-3 on CD8T cells in smear-positive tuberculosis patients was significantly higher than that in sputum smear-negative tuberculosis patients (P < 0.05). LAG-3 expression on CD8T cells was negatively correlated with the presence of lung lesions (P < 0.05). After stimulation with a tuberculosis-specific antigen, the expression of LAG-3 on tuberculosis-specific CD8T cells was also upregulated, and LAG-3-expressing CD8T cells showed reduced production of IFN-γ, decreased activation, and lower proliferation, while the function of CD8T cells was restored when LAG-3 signaling was blocked.
This study further explored the relationship between immune exhaustion caused by LAG-3 and immune escape of Mycobacterium tuberculosis and revealed that the elevated expression of LAG-3 on CD8T cells correlates with functional defects of CD8T cells and the severity of pulmonary TB.
淋巴细胞激活基因 3（LAG-3）在调节 T 细胞反应和诱导外周耐受方面发挥重要作用。本研究旨在探讨 LAG-3 与活动性肺结核（ATB）的关系以及 LAG-3 阻断对 CD8T 细胞的影响。
采用流式细胞术检测 ATB 患者外周血和支气管肺泡灌洗液中 CD4T 和 CD8T 细胞上 LAG-3 的表达，探讨 LAG-3 与 ATB 的关系。
ATB 患者 CD4T 和 CD8T 细胞上 LAG-3 的表达增加（P<0.001），高表达 LAG-3 的 CD8T 细胞与痰培养结果相关（P<0.05）。我们进一步分析了 CD8T 细胞中 LAG-3 的表达与结核病严重程度的关系，发现涂阳肺结核患者 CD8T 细胞上 LAG-3 的表达明显高于涂阴肺结核患者（P<0.05）。CD8T 细胞上 LAG-3 的表达与肺部病变的存在呈负相关（P<0.05）。在结核特异性抗原刺激后，结核特异性 CD8T 细胞上 LAG-3 的表达也上调，表达 LAG-3 的 CD8T 细胞 IFN-γ 的产生减少，激活降低，增殖减少，而阻断 LAG-3 信号通路可恢复 CD8T 细胞的功能。
本研究进一步探讨了 LAG-3 引起的免疫衰竭与结核分枝杆菌免疫逃逸之间的关系，揭示了 CD8T 细胞上 LAG-3 的高表达与 CD8T 细胞的功能缺陷和肺结核的严重程度相关。
