Background Mycobacterium tuberculosis (Mtb) adapts many strategies to persist and replicate inside human tissue. One such strategy is the manipulation of CD4+ TH cells for subset interconversion to regulatory subsets. The aim of the present study is to get an insight of dynamic changes of CD4+ TH cells to regulatory subsets, CD4+ CD25+ forkhead box P3 (Foxp3)+ T-cells and CD4+ CD25+ Foxp3+ programmed death molecule-1 (Foxp3+) T-cells, in peripheral blood in Mtb-infected individuals and healthy contacts in a high-burden setting from Assam, Northeast India. Materials and Methods A case-control study was conducted in newly diagnosed active pulmonary tuberculosis (APTBs) patients and 2 sets of controls: (i) individuals infected with latent tuberculosis infection (LTBI) and (ii) healthy close tuberculosis healthy contacts (HCs). The frequencies of different subsets of CD4+ cells with regulatory markers were measured in peripheral blood in 3 groups of study participants. Results and Observations Frequencies of CD4+ CD25+ Foxp3+ T-cells (1.84 ± 1.40 vs. 4.32 ± 1.82 vs. 11.30 ± 3.66), CD4+ CD25+ Foxp3+ PD1+ T-cells (0.37 ± 1.28 vs. 2.99 ± 3.69 vs. 14.54 ± 5.10) and ligand (PD-L1)-positive CD4+ TH cells (0.80 ± 0.45 vs. 2.28 ± 0.95 vs. 7.13 ± 2.02) were significantly increased from HCs to LTBIs to APTB patients, respectively (P < 0.0001). No significant changes in frequencies of total CD4+ cells were observed between APTBs (29.51 ± 11.93), LTBIs (29.23 ± 8.16) and HCs (28.16 ± 9.73) whereas the mean ratios of CD4+ to CD4+ CD25+ FoxP3+ were significantly decreased from 34.34 ± 47.56 in HCs to 7.96 ± 5.8 in LTBIs to 3.12 ± 2.58 in APTBs (P < 0.0001). Significant decrease in mean ratios of CD4+ CD25+ FoxP3+ to CD4+ CD25+ FoxP3+ PD1+ were also observed from 4.97 ± 1.09 in HCs to 1.44 ± 0.49 in LTBIs to 0.78 ± 0.72 in APTBs. Conclusion CD4+ TH cells change dynamically to regulatory subsets depending on the status of infection and a shift of response towards excessive regulatory T-cells, and PD-1/PD-L1 production may help in the development of active infection in latently infected individuals. These immunological parameters may be used, as potential biomarkers to see the changing dynamics of Mtb infection.

中文翻译：

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印度东北部阿萨姆邦高负担环境中结核分枝杆菌感染者和健康接触者外周血中 CD4+ TH 细胞调节亚群的频率。


背景 结核分枝杆菌 (Mtb) 采用多种策略在人体组织内持续存在和复制。其中一种策略是操纵 CD4+ TH 细胞将亚群相互转化为调节亚群。本研究的目的是深入了解 CD4+ TH 细胞向调节亚群、CD4+ CD25+ 叉头盒 P3 (Foxp3)+ T 细胞和 CD4+ CD25+ Foxp3+ 程序性死亡分子-1 (Foxp3+) T 细胞的动态变化，印度东北部阿萨姆邦高负担环境中结核分枝杆菌感染者和健康接触者的外周血中存在这种情况。材料和方法 在新诊断的活动性肺结核 (APTB) 患者和 2 组对照中进行病例对照研究：(i) 潜伏性结核感染者 (LTBI) 和 (ii) 健康的结核病密切接触者 (HC) 。测量了 3 组研究参与者的外周血中具有调节标记的不同 CD4+ 细胞亚群的频率。结果和观察 CD4+ CD25+ Foxp3+ T 细胞的频率（1.84 ± 1.40 vs. 4.32 ± 1.82 vs. 11.30 ± 3.66）、CD4+ CD25+ Foxp3+ PD1+ T 细胞（0.37 ± 1.28 vs. 2.99 ± 3.69 vs. 14.54 ± 5.10）和配体 (PD-L1) 阳性 CD4+ TH 细胞 (0.80 ± 0.45 vs. 2.28 ± 0.95 vs. 7.13 ± 2.02) 从 HC 到 LTBI 再到 APTB 患者分别显着增加 (P < 0.0001)。 APTB (29.51 ± 11.93)、LTBI (29.23 ± 8.16) 和 HC (28.16 ± 9.73) 之间总 CD4+ 细胞频率没有观察到显着变化，而 CD4+ 与 CD4+ CD25+ FoxP3+ 的平均比率从 34.34 ± 47.56 显着下降。 LTBI 中的 HC 为 7.96 ± 5.8，APTB 中的 HC 为 3.12 ± 2.58 (P < 0.0001)。还观察到 HC 中 CD4+ CD25+ FoxP3+ 与 CD4+ CD25+ FoxP3+ PD1+ 的平均比率显着下降，从 4.97 ± 1.09 降至 1。LTBI 为 44 ± 0.49，APTB 为 0.78 ± 0.72。结论 CD4+ TH 细胞根据感染状态动态变化为调节亚群，以及向过度调节 T 细胞的反应转变，而 PD-1/PD-L1 的产生可能有助于潜伏感染个体发生活动性感染。这些免疫学参数可用作潜在的生物标志物，以观察结核分枝杆菌感染的动态变化。