Mapping and role of T cell response in SARS-CoV-2–infected mice

• Published in: The Journal of experimental medicine Vol. 218; no. 4
• Main Authors: Zhuang, Zhen, Lai, Xiaomin, Sun, Jing, Chen, Zhao, Zhang, Zhaoyong, Dai, Jun, Liu, Donglan, Li, Yuming, Li, Fang, Wang, Yanqun, Zhu, Airu, Wang, Junxiang, Yang, Wenhui, Huang, Jicheng, Li, Xiaobo, Hu, Lingfei, Wen, Liyan, Zhuo, Jianfen, Zhang, Yanjun, Chen, Dingbin, Li, Suxiang, Huang, Shuxiang, Shi, Yongxia, Zheng, Kui, Zhong, Nanshan, Zhao, Jingxian, Zhou, Dongsheng, Zhao, Jincun
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 05.04.2021
• Subjects: Angiotensin-Converting Enzyme 2 - genetics; Angiotensin-Converting Enzyme 2 - metabolism; Animals; Antibodies, Neutralizing - blood; CD4-Positive T-Lymphocytes - virology; CD8-Positive T-Lymphocytes - virology; Chlorocebus aethiops; COVID-19 - immunology; Cross Reactions; Epitope Mapping; Epitopes, T-Lymphocyte - immunology; Host-Pathogen Interactions - physiology; Infectious Disease and Host Defense; Interferon Type I - immunology; Interferon Type I - metabolism; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Middle East Respiratory Syndrome Coronavirus - immunology; SARS-CoV-2 - immunology; SARS-CoV-2 - pathogenicity; Severe acute respiratory syndrome-related coronavirus - immunology; T-Lymphocytes - immunology; T-Lymphocytes - virology; Technical Advances and Resources; Vero Cells
• ISSN: 0022-1007; 1540-9538; 1540-9538
• DOI: 10.1084/jem.20202187

Virus-specific T cells play essential roles in protection against multiple virus infections, including SARS-CoV and MERS-CoV. While SARS-CoV-2–specific T cells have been identified in COVID-19 patients, their role in the protection of SARS-CoV-2–infected mice is not established. Here, using mice sensitized for infection with SARS-CoV-2 by transduction with an adenovirus expressing the human receptor (Ad5-hACE2), we identified SARS-CoV-2–specific T cell epitopes recognized by CD4+ and CD8+ T cells in BALB/c and C57BL/6 mice. Virus-specific T cells were polyfunctional and were able to lyse target cells in vivo. Further, type I interferon pathway was proved to be critical for generating optimal antiviral T cell responses after SARS-CoV-2 infection. T cell vaccination alone partially protected SARS-CoV-2–infected mice from severe disease. In addition, the results demonstrated cross-reactive T cell responses between SARS-CoV and SARS-CoV-2, but not MERS-CoV, in mice. Understanding the role of the T cell response will guide immunopathogenesis studies of COVID-19 and vaccine design and validation.