新冠,T细胞 z-bio 2025-02-11 250

Response and function of SARS-CoV-2-specific T cells in bronchoalveolar lavage fluid　

　　Under the support of the National Natural Science Foundation of China (Grant No. 82495200, 82495203, 82025001, 82201933, 82201932), the team of Professor Zhao Jincun, Professor Zhao Jingxian and Academician Zhong Nanshan from the First Affiliated Hospital of Guangzhou Medical University/Guangzhou National Laboratory made progress in the research on the characteristics and functions of virus specific T cells in the lungs of COVID-19 patients. The relevant research achievements are entitled "Robust mycosal SARS-CoV-2-specific T cells effectively combat COVID-19 and establish multi-functional resident memory in patient lungs", which was published online in Nature Immunology on January 28, 2025. The link to the paper is: https://www.nature.com/articles/s41590-024-02072-9 .

　　The COVID-19 epidemic has had a huge impact on global public health. Although vaccination has played an important role in controlling the epidemic situation, breakthrough infections still occur from time to time, suggesting that we need to understand more about the human immune response, especially the role of lung regional immune response in COVID-19 infection. Although the research on novel coronavirus (SARS-CoV-2) continues to deepen, many key links of the lung immune response, especially the characteristics and functions of SARS-CoV-2 specific T cells in the lung, have not been thoroughly studied before.

　　The research team included 159 COVID-19 patients and collected 122 bronchoalveolar lavage fluid (BALF) samples and 280 blood samples (including 27 pairs of bronchoalveolar lavage fluid and blood samples from 24 patients). A comprehensive analysis of SARS-CoV-2-specific T cells in the lung airway and periphery was conducted using techniques such as single-cell transcriptome sequencing (scRNA seq), single-cell T cell receptor (TCR) sequencing, and high-dimensional flow cytometry. The research team found that the number of SARS-CoV-2-specific T cells in the bronchoalveolar lavage fluid of patients is closely related to reduced viral load, reduced systemic inflammation, and improved respiratory function, indicating that respiratory mucosal T cells play an important role in controlling virus replication and reducing the severity of COVID-19 (Figure). Moreover, compared with peripheral blood samples, the specific T cells mentioned above exhibit stronger abilities to activate, proliferate, and secrete multiple cytokines, and exhibit unique metabolic characteristics mainly based on glycolysis, which can provide support for the effector function of activated T cells. Further transcriptional analysis revealed that interferon response, T cell activation, inflammation, tissue migration, proliferation, and metabolism related pathways were significantly upregulated in this type of virus specific T cells. After virus clearance, the aforementioned T cells maintain a multifunctional tissue resident memory phenotype, which can quickly respond to reinfection and provide long-term protection against SARS-CoV-2. In addition, there was no significant difference in the response of virus specific T cells in the lung region to SARS CoV-2 infection between the individuals who received intramuscular injection of COVID-19 inactivated vaccine and those who did not receive the vaccine, suggesting that intramuscular injection of vaccine may be difficult to establish effective T cell immune memory in the airway, suggesting the necessity of developing a mucosal vaccine that can induce local immunity in the respiratory tract.

　　This study reveals the important role of SARS-CoV-2-specific T cells in lung airway mucosa in COVID-19, providing a basis for developing more effective mucosal vaccines to combat COVID-19 and other respiratory infections.