tetano
Editor, Senior Moderator
Nat Immunol
. 2025 Jan 28.
doi: 10.1038/s41590-024-02072-9. Online ahead of print. Robust mucosal SARS-CoV-2-specific T cells effectively combat COVID-19 and establish polyfunctional resident memory in patient lungs
Airu Zhu[SUP] #[/SUP][SUP] 1 [/SUP], Zhao Chen[SUP] #[/SUP][SUP] 1 [/SUP], Qihong Yan[SUP] #[/SUP][SUP] 1 [/SUP], Mei Jiang[SUP] #[/SUP][SUP] 1 [/SUP], Xuesong Liu[SUP] #[/SUP][SUP] 1 2 [/SUP], Zhengtu Li[SUP] #[/SUP][SUP] 1 [/SUP], Na Li[SUP] #[/SUP][SUP] 3 [/SUP], Chunli Tang[SUP] #[/SUP][SUP] 1 [/SUP], Wenhua Jian[SUP] #[/SUP][SUP] 1 [/SUP], Jiangping He[SUP] 4 [/SUP], Lan Chen[SUP] 1 4 [/SUP], Jinling Cheng[SUP] 1 [/SUP], Canjie Chen[SUP] 1 [/SUP], Tian Tang[SUP] 1 [/SUP], Zhiwei Xu[SUP] 1 [/SUP], Qingtao Hu[SUP] 1 5 [/SUP], Fang Li[SUP] 1 [/SUP], Yanqun Wang[SUP] 1 [/SUP], Jing Sun[SUP] 1 [/SUP], Zhen Zhuang[SUP] 1 [/SUP], Liyan Wen[SUP] 1 [/SUP], Jianfen Zhuo[SUP] 1 [/SUP], Donglan Liu[SUP] 1 [/SUP], Yanjun Zhang[SUP] 1 [/SUP], Xiaofang Huang[SUP] 1 [/SUP], Suxiang Li[SUP] 1 [/SUP], Qiuhui Zeng[SUP] 1 [/SUP], Fangli Chen[SUP] 1 [/SUP], Liang Zhou[SUP] 1 2 [/SUP], Dongdong Liu[SUP] 1 2 [/SUP], Changhao Zhong[SUP] 1 [/SUP], Yu Chen[SUP] 1 [/SUP], Shiyue Li[SUP] 1 [/SUP], Kangli Liang[SUP] 6 [/SUP], Na Zhong[SUP] 7 [/SUP], Xinmei Zhang[SUP] 7 [/SUP], Jiekai Chen[SUP] 8 [/SUP], Xiaobo Chen[SUP] 9 [/SUP], Yonghao Xu[SUP] 10 11 12 [/SUP], Nanshan Zhong[SUP] 13 14 [/SUP], Jingxian Zhao[SUP] 15 16 [/SUP], Jincun Zhao[SUP] 17 18 19 20 [/SUP]
Affiliations
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.
. 2025 Jan 28.
doi: 10.1038/s41590-024-02072-9. Online ahead of print. Robust mucosal SARS-CoV-2-specific T cells effectively combat COVID-19 and establish polyfunctional resident memory in patient lungs
Airu Zhu[SUP] #[/SUP][SUP] 1 [/SUP], Zhao Chen[SUP] #[/SUP][SUP] 1 [/SUP], Qihong Yan[SUP] #[/SUP][SUP] 1 [/SUP], Mei Jiang[SUP] #[/SUP][SUP] 1 [/SUP], Xuesong Liu[SUP] #[/SUP][SUP] 1 2 [/SUP], Zhengtu Li[SUP] #[/SUP][SUP] 1 [/SUP], Na Li[SUP] #[/SUP][SUP] 3 [/SUP], Chunli Tang[SUP] #[/SUP][SUP] 1 [/SUP], Wenhua Jian[SUP] #[/SUP][SUP] 1 [/SUP], Jiangping He[SUP] 4 [/SUP], Lan Chen[SUP] 1 4 [/SUP], Jinling Cheng[SUP] 1 [/SUP], Canjie Chen[SUP] 1 [/SUP], Tian Tang[SUP] 1 [/SUP], Zhiwei Xu[SUP] 1 [/SUP], Qingtao Hu[SUP] 1 5 [/SUP], Fang Li[SUP] 1 [/SUP], Yanqun Wang[SUP] 1 [/SUP], Jing Sun[SUP] 1 [/SUP], Zhen Zhuang[SUP] 1 [/SUP], Liyan Wen[SUP] 1 [/SUP], Jianfen Zhuo[SUP] 1 [/SUP], Donglan Liu[SUP] 1 [/SUP], Yanjun Zhang[SUP] 1 [/SUP], Xiaofang Huang[SUP] 1 [/SUP], Suxiang Li[SUP] 1 [/SUP], Qiuhui Zeng[SUP] 1 [/SUP], Fangli Chen[SUP] 1 [/SUP], Liang Zhou[SUP] 1 2 [/SUP], Dongdong Liu[SUP] 1 2 [/SUP], Changhao Zhong[SUP] 1 [/SUP], Yu Chen[SUP] 1 [/SUP], Shiyue Li[SUP] 1 [/SUP], Kangli Liang[SUP] 6 [/SUP], Na Zhong[SUP] 7 [/SUP], Xinmei Zhang[SUP] 7 [/SUP], Jiekai Chen[SUP] 8 [/SUP], Xiaobo Chen[SUP] 9 [/SUP], Yonghao Xu[SUP] 10 11 12 [/SUP], Nanshan Zhong[SUP] 13 14 [/SUP], Jingxian Zhao[SUP] 15 16 [/SUP], Jincun Zhao[SUP] 17 18 19 20 [/SUP]
Affiliations
- PMID: 39875584
- DOI: 10.1038/s41590-024-02072-9
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.