Emory Vaccine Center, Emory University, Atlanta, Georgia, USA.
Tulane National Primate Research Center, Tulane University School of Medicine, Covington, Louisiana, USA.
JCI Insight. 2020 Jul 23;5(14):137858. doi: 10.1172/jci.insight.137858.
Mycobacterium tuberculosis-specific (M. tuberculosis-specific) T cell responses associated with immune control during asymptomatic latent tuberculosis infection (LTBI) remain poorly understood. Using a nonhuman primate aerosol model, we studied the kinetics, phenotypes, and functions of M. tuberculosis antigen-specific T cells in peripheral and lung compartments of M. tuberculosis-infected asymptomatic rhesus macaques by longitudinally sampling blood and bronchoalveolar lavage, for up to 24 weeks postinfection. We found substantially higher frequencies of M. tuberculosis-specific effector and memory CD4+ and CD8+ T cells producing IFN-γ in the airways compared with peripheral blood, and these frequencies were maintained throughout the study period. Moreover, M. tuberculosis-specific IL-17+ and IL-17+IFN-γ+ double-positive T cells were present in the airways but were largely absent in the periphery, suggesting that balanced mucosal Th1/Th17 responses are associated with LTBI. The majority of M. tuberculosis-specific CD4+ T cells that homed to the airways expressed the chemokine receptor CXCR3 and coexpressed CCR6. Notably, CXCR3+CD4+ cells were found in granulomatous and nongranulomatous regions of the lung and inversely correlated with M. tuberculosis burden. Our findings provide insights into antigen-specific T cell responses associated with asymptomatic M. tuberculosis infection that are relevant for developing better strategies to control TB.
结核分枝杆菌特异性（M. tuberculosis-specific）T 细胞反应与无症状潜伏性结核感染（LTBI）期间的免疫控制有关，但仍了解甚少。我们使用非人灵长类动物气溶胶模型，通过对感染结核分枝杆菌的无症状恒河猴进行纵向采血和支气管肺泡灌洗，在感染后长达 24 周的时间内，研究了外周血和肺组织中结核分枝杆菌抗原特异性 T 细胞的动力学、表型和功能。我们发现，与外周血相比，气道中产生 IFN-γ的结核分枝杆菌特异性效应和记忆 CD4+和 CD8+T 细胞的频率要高得多，而且这些频率在整个研究期间都保持不变。此外，气道中存在结核分枝杆菌特异性的 IL-17+和 IL-17+IFN-γ+双阳性 T 细胞，但在外周血中则很少见，这表明平衡的黏膜 Th1/Th17 反应与 LTBI 有关。归巢至气道的结核分枝杆菌特异性 CD4+T 细胞中，大多数表达趋化因子受体 CXCR3，并共表达 CCR6。值得注意的是，CXCR3+CD4+细胞存在于肺部的肉芽肿和非肉芽肿区域，并与结核分枝杆菌负担呈负相关。我们的研究结果为无症状结核分枝杆菌感染相关的抗原特异性 T 细胞反应提供了新的见解，这对于开发更好的控制结核病的策略具有重要意义。
