Chen Zhen-Yan, Wang Lei, Gu Ling, Qu Rong, Lowrie Douglas B, Hu Zhidong, Sha Wei, Fan Xiao-Yong
Shanghai Public Health Clinical Center, Key Laboratory of Medical Molecular Virology of MOE/MOH, Fudan University, Shanghai, China.
Shanghai Pulmonary Hospital, Tongji University, Shanghai, China.
Front Microbiol. 2020 Aug 7;11:1901. doi: 10.3389/fmicb.2020.01901. eCollection 2020.
CD69 is a biomarker of T-cell activation status, but its activation status in human () infection remains elusive.
A set of cohorts of patients with different tuberculosis (TB) infection status including active TB patients (ATB), latent tuberculous infection patients (LTBI) and close contacts (CCs) of ATB was designed, and the expression profiles of CD69 and several T-cell markers were determined on antigen-stimulated T cells by flow cytometry.
The frequencies of CD4 and CD8 T cells were both comparable among -infected individuals including ATB and LTBI, which guaranteed the consistency of the background level. A t-Distributed Stochastic Neighbor Embedding (tSNE) analysis on a panel of six phenotypic markers showed a unique color map axis gated on T cells in the CCs group compared with ATB and LTBI populations. By further gating on cells positive for each individual marker and then overlaying those events on top of the tSNE plots, their distribution suggested that some markers were expressed differently in the CCs group. Further analysis showed that the expression levels of CD69 on both CD4 and CD8 T cells were significantly lower in the CCs group, especially in interferon-γ-responding T cells.
Our findings suggest that the T-cell activation status of CD69 is associated with infection and may have the potential to distinguish LTBI from those populations who have been exposed continuously to but have not become infected.
CD69是T细胞活化状态的生物标志物,但其在人类()感染中的活化状态仍不清楚。
设计了一组具有不同结核(TB)感染状态的患者队列,包括活动性结核病患者(ATB)、潜伏性结核感染患者(LTBI)和ATB的密切接触者(CCs),通过流式细胞术测定抗原刺激的T细胞上CD69和几种T细胞标志物的表达谱。
在包括ATB和LTBI在内的感染个体中,CD4和CD8 T细胞的频率相当,这保证了背景水平的一致性。对一组六个表型标志物进行的t分布随机邻域嵌入(tSNE)分析显示,与ATB和LTBI群体相比,CCs组中以T细胞为门控的独特颜色图谱轴。通过进一步对每个个体标志物阳性的细胞进行门控,然后将这些事件叠加在tSNE图上,它们的分布表明某些标志物在CCs组中的表达不同。进一步分析表明,CCs组中CD4和CD8 T细胞上CD69的表达水平均显著降低,尤其是在干扰素-γ反应性T细胞中。
我们的研究结果表明,CD69的T细胞活化状态与感染有关,并且可能有潜力将LTBI与那些持续接触但未感染的人群区分开来。