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中国防痨杂志 ›› 2026, Vol. 48 ›› Issue (5): 621-630.doi: 10.19982/j.issn.1000-6621.20250433

• 论著 • 上一篇    下一篇

结核分枝杆菌感染不同状态T淋巴细胞表面共信号分子的表达及临床意义

仝静1, 刘珂伟1, 郭灿2, 石金1, 逄宇3(), 高孟秋1(), 李姗姗3()   

  1. 1首都医科大学附属北京胸科医院结核二区/北京市结核病胸部肿瘤研究所, 北京 101149
    2新乡医学院第一附属医院结核二科, 新乡 453100
    3首都医科大学附属北京胸科医院/北京市结核病胸部肿瘤研究所细菌免疫室, 北京 101149
  • 收稿日期:2025-11-06 出版日期:2026-05-10 发布日期:2026-04-27
  • 通信作者: 逄宇,高孟秋,李姗姗 E-mail:pangyupound@163.com;gaomqwdm@aliyun.com;lss9011@126.com
  • 基金资助:
    国家自然科学基金(82202530);首都医科大学附属北京胸科医院中青年人才培养工程(ZQNQN202610);首都医科大学临床专科学院(系)培养基金开放课题(CCMU2024ZKYXZ004)

Expression and clinical significance of co-signaling molecules on surface of T lymphocytes in different states of Mycobacterium tuberculosis infection

Tong Jing1, Liu Kewei1, Guo Can2, Shi Jin1, Pang Yu3(), Gao Mengqiu1(), Li Shanshan3()   

  1. 1Department of Tuberculosis Ⅱ, Beijing Chest Hospital, Capital Medical University/Beijing Institute of Tuberculosis and Thoracic Tumor, Beijing 101149, China
    2Department of Tuberculosis Ⅱ, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang 453100, China
    3Department of Bacterial Immunology, Beijing Chest Hospital, Capital Medical University/Beijing Institute of Tuberculosis and Thoracic Tumor, Beijing 101149, China
  • Received:2025-11-06 Online:2026-05-10 Published:2026-04-27
  • Contact: Pang Yu,Gao Mengqiu,Li Shanshan E-mail:pangyupound@163.com;gaomqwdm@aliyun.com;lss9011@126.com
  • Supported by:
    National Natural Science Foundation of China(82202530);Capital Medical University Affiliated Beijing Chest Hospital Young and Middle-aged Talent Training Program(ZQNQN202610);Capital Medical University Clinical College (Department) Training Fund Open Research Project(CCMU2024ZKYXZ004)

摘要:

目的: 分析结核分枝杆菌感染不同状态人群外周血T淋巴细胞亚群比例、表面共信号分子表达情况及其临床意义。方法: 采用前瞻性研究方法,选取2023年8月3日至2024年10月30日首都医科大学附属北京胸科医院符合入组标准的22例菌阳肺结核患者(TB组)、20例结核分枝杆菌潜伏感染(latent tuberculosis infection, LTBI)者(LTBI组),以及同期进行健康检查的22名健康者(HC组),通过全光谱多参数流式细胞术分析3组人群外周血T淋巴细胞比例,以及T淋巴细胞表面13个共信号分子的表达分布。结果: TB组CD3+和CD4+ T淋巴细胞水平[分别为(53.23±16.15)%和(33.06±9.58)%]均明显低于HC组[分别为(65.59±13.94)%和(40.39±11.01)%],CD8+ T淋巴细胞水平[(16.88±7.59)%]分别低于HC组[(24.07±8.86)%]和LTBI组[(24.56±7.09)%],差异均有统计学意义(q=4.156,P=0.013;q=3.594,P=0.036;q=4.267,P=0.010;q=4.450,P=0.007)。在CD4+ T淋巴细胞中,TB组CTLA-4表达量[0.42%(0.21%,1.92%)]明显高于HC组[0.20%(0.14%,0.34%)]和LTBI组[0.14%(0.07%,0.20%)],CD160表达量[0.00%(0.01%,0.05%)]明显低于HC组[0.08%(0.01%,0.17%)],LTBI组TIGIT表达量[(20.87±6.11)%]明显高于HC组[(13.93±5.28)%]和TB组[(12.92±5.13)%],差异均有统计学意义(Z=2.503,P=0.037;Z=4.548,P<0.001;Z=2.447,P=0.043;q=5.877,P<0.001;q=4.903,P=0.003)。在CD8+ T淋巴细胞中,TB组CTLA-4表达量[1.03%(0.22%,1.63%)]明显高于HC组[0.10%(0.04%,0.46%)]和LTBI组[0.08%(0.05%,0.12%)],差异均有统计学意义(Z=3.477,P=0.002;Z=4.279,P<0.001)。共刺激信号分子中,TB组和LTBI组CD4+ T淋巴细胞中的GITR的表达量[分别为2.34%(1.36%,5.20%)和2.01%(1.64%,3.80%)]均明显高于HC组[1.48%(0.88%,1.64%)],TB组CD4+ T淋巴细胞中的CD40L、CD8+ T淋巴细胞中的OX40和ICOS表达量[分别为0.07%(0.03%,0.10%)、0.16%(0.05%,0.46%)、7.28%(4.46%,16.56%)]均明显高于HC组[分别为0.02%(0.01%,0.05%)、0.03%(0.01%,0.09%)、2.97%(1.48%,5.54%)],差异均有统计学意义(Z=2.834,P=0.014;Z=3.027,P=0.007;Z=2.825,P=0.014;Z=3.655,P<0.001;Z=3.364,P=0.002)。结论: 结核分枝杆菌感染者尤其是活动性肺结核患者外周血T淋巴细胞比例存在失衡,同时其T淋巴细胞表面部分共信号分子表达也发生改变,提示该类患者存在免疫抑制或T淋巴细胞耗竭,可能为结核病诊断、宿主导向的免疫治疗和结核病新疫苗的研发提供新的方向。

关键词: 分枝杆菌感染, 衔接蛋白质类,信号转导, 淋巴细胞亚群, 免疫, 细胞, 免疫因子类

Abstract:

Objective: To detect the expression of T lymphocyte subsets and T cell surface co-signaling molecules in peripheral blood of populations with different Mycobacterium tuberculosis infection statuses and analyze their clinical significance. Methods: A prospective study design was employed. A total of 22 patients with pulmonary tuberculosis (TB group), 20 individuals with latent Mycobacterium tuberculosis infection (LTBI group), who met the inclusion and exclusion criteria, were enrolled at Beijing Chest Hospital Affiliated to Capital Medical University between August 3, 2023 and October 30, 2024. In addition, 22 healthy volunteers (HC group) who underwent physical examination during the same period were recruited as controls. Peripheral blood mononuclear cells from the three groups were analyzed using full-spectrum multiparametric flow cytometry to investigate the proportions of T lymphocytes and the distributions of 13 co-signaling molecules on T cells surface among different populations. Results: The levels of CD3+ T cells in the TB group ((53.23±16.15) %) and CD4+ T cells ((33.06±9.58) %) were significantly lower than those in the HC group ((65.59±13.94) % and (40.39±11.01) % respectively), and the level of CD8+ T cells ((16.88±7.59) %) was lower than that in the HC group ((24.07±8.86) %) and the LTBI group ((24.56±7.09) %), the differences were statistically significant (q=4.156, P=0.013; q=3.594, P=0.036; q=4.267, P=0.010; q=4.450, P=0.007). In CD4+ T cells, the expression level of CTLA-4 in the TB group (0.42% (0.21%, 1.92%)) was significantly higher than that in the HC group (0.20% (0.14%, 0.34%)) and the LTBI group (0.14% (0.07%, 0.20%)), the expression level of CD160 in the TB group (0.00% (0.01%, 0.05%)) was significantly lower than that in the HC group (0.08% (0.01%, 0.17%), the proportion of TIGIT in the LTBI group ((20.87±6.11) %) was significantly higher than that in the HC group ((13.93±5.28) %) and the TB group ((12.92±5.13) %), and the differences were all statistically significant (Z=2.503, P=0.037; Z=4.548, P<0.001; Z=2.447, P=0.043; q=5.877, P<0.001; q=4.903, P=0.003). In CD8+ T cells, the expression level of CTLA-4 in the TB group (1.03% (0.22%, 1.63%)) was significantly higher than that in the HC group (0.10% (0.04%, 0.46%)) and the LTBI group (0.08% (0.05%, 0.12%)), and the differences were statistically significant (Z=3.477, P=0.002; Z=4.279, P<0.001). Among the co-stimulatory signaling molecules, the expression levels of GITR of CD4+ T cells in the TB group and the LTBI group (2.34% (1.36%, 5.20%) and 2.01% (1.64%, 3.80%) respectively) were significantly higher than that in the HC group (1.48% (0.88%, 1.64%)), and the proportions of CD40L of CD4+ T cells, OX40 and ICOS of CD8+ T cells in the TB group (0.07% (0.03%, 0.10%), 0.16% (0.05%, 0.46%) and 7.28% (4.46%, 16.56%) respectively) were significantly higher than those in the HC group (0.02% (0.01%, 0.05%), 0.03% (0.01%, 0.09%), and 2.97% (1.48%, 5.54%) respectively), and the differences were all statistically significant (Z=2.834, P=0.014; Z=3.027, P=0.007; Z=2.825, P=0.014; Z=3.655, P<0.001; Z=3.364, P=0.002). Conclusion: The proportion of T lymphocytes in the peripheral blood of patients infected with Mycobacterium tuberculosis, especially those with active pulmonary tuberculosis, is imbalanced. At the same time, the expression of co-signaling molecules on the surface of T cells also changes, suggesting that such patients have immunosuppression or may have T cell exhaustion. This may provide new directions for development of tuberculosis diagnosis, host-directed immunotherapy, and new tuberculosis vaccine.

Key words: Mycobacterium infections, Adaptor proteins, signal transducing, Lymphocyte subsets, Immunity, cellular, Immunologic factors

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