Article
作者: Xu, Yonghao ; Zhong, Changhao ; Chen, Fangli ; Zhong, Na ; Xu, Zhiwei ; Chen, Lan ; Chen, Jiekai ; Tang, Tian ; Liang, Kangli ; Chen, Zhao ; Zhang, Yanjun ; Liu, Dongdong ; Li, Na ; Cheng, Jinling ; Zhou, Liang ; Yan, Qihong ; Li, Zhengtu ; Wen, Liyan ; Li, Fang ; Zhuo, Jianfen ; Zhao, Jincun ; Tang, Chunli ; Li, Suxiang ; Chen, Xiaobo ; Zhuang, Zhen ; Zeng, Qiuhui ; Liu, Donglan ; Li, Shiyue ; Chen, Canjie ; He, Jiangping ; Zhao, Jingxian ; Zhu, Airu ; Chen, Yu ; Huang, Xiaofang ; Zhang, Xinmei ; Wang, Yanqun ; Jian, Wenhua ; Jiang, Mei ; Sun, Jing ; Liu, Xuesong ; Zhong, Nanshan ; Hu, Qingtao
Mucosal antigen-specific T cells are pivotal for pathogen clearance and immune modulation in respiratory infections. Dysregulated T cell responses exacerbate coronavirus disease 2019 severity, marked by cytokine storms and respiratory failure. Despite extensive description in peripheral blood, the characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cells in the lungs remain elusive. Here we conducted integrated single-cell profiling of SARS-CoV-2-specific T cells in 122 bronchoalveolar lavage fluid (BALF) and 280 blood samples from 159 patients, including 27 paired BALF and blood samples from 24 patients. SARS-CoV-2-specific T cells were robustly elicited in BALF irrespective of prior vaccination, correlating with diminished viral loads, lessened systemic inflammation and improved respiratory function. SARS-CoV-2-specific T cells in BALF exhibited profound activation, along with proliferative and multi-cytokine-producing capabilities and a glycolysis-driven metabolic signature, which were distinct from those observed in peripheral blood mononuclear cells. After viral clearance, these specific T cells maintained a polyfunctional tissue-resident memory phenotype, highlighting their critical roles in infection control and long-term protection.