State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Guangzhou Customs District Technology Center, Guangzhou, China.
J Exp Med. 2021 Apr 5;218(4). 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.
病毒特异性 T 细胞在预防多种病毒感染中发挥着重要作用，包括严重急性呼吸综合征冠状病毒（SARS-CoV）和中东呼吸综合征冠状病毒（MERS-CoV）。虽然在 COVID-19 患者中已经鉴定出了针对 SARS-CoV-2 的 T 细胞，但它们在保护感染 SARS-CoV-2 的小鼠中的作用尚未确定。在这里，我们使用通过表达人受体的腺病毒（Ad5-hACE2）转导使小鼠对 SARS-CoV-2 感染敏感的方法，鉴定了 BALB/c 和 C57BL/6 小鼠中 CD4+和 CD8+T 细胞识别的 SARS-CoV-2 特异性 T 细胞表位。病毒特异性 T 细胞具有多功能性，能够在体内裂解靶细胞。此外，研究证明Ⅰ型干扰素途径对于 SARS-CoV-2 感染后产生最佳抗病毒 T 细胞反应至关重要。单独的 T 细胞疫苗接种可部分保护 SARS-CoV-2 感染的小鼠免受严重疾病的侵害。此外，结果表明，在小鼠中，SARS-CoV 和 SARS-CoV-2 之间存在交叉反应性 T 细胞反应，但与 MERS-CoV 没有交叉反应性。了解 T 细胞反应的作用将指导 COVID-19 的免疫发病机制研究以及疫苗的设计和验证。
