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

Abstract

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.

Activation or exhaustion of CD8+ T cells in patients with COVID-19

“…Limited viral clearance in the respiratory tract was observed in CD8 + -depleted convalescent rhesus macaques upon SARS-CoV-2 rechallenge, implying that memory CD8 + T cells are required for the clearance of SARS-CoV-2 [ 18 ]. Furthermore, T-cell vaccination that does not elicit neutralizing antibodies partially protects SARS-CoV-2-infected mice from severe disease [ 19 ].…”

“…It is now clear that SARS-CoV-2-specific CD8 + T-cell responses are detected in the acute and convalescent phases of COVID-19 [ 12 – 17 ]. In addition, recent studies using animal models have reported that CD8 + T cells contribute to protection from the development of severe COVID-19 [ 18 , 19 ].…”

Phenotypes and Functions of SARS-CoV-2-Reactive T Cells

“…In a rhesus macaque model, CD8-depleted convalescent animals exhibited limited viral clearance upon SARS-CoV-2 re-challenge, suggesting that memory CD8 + T cells contribute to viral clearance during SARS-CoV-2 re-infection (McMahan et al, 2021). Furthermore, T-cell vaccination partially protected hosts from severe disease in a mouse model of SARS-CoV-2 infection (Zhuang et al, 2021).…”

Adaptive immune determinants of viral clearance and protection in mouse models of SARS-CoV-2

“…No reuse allowed without permission. (27,28). We found that both groups developed similar levels of spike specific IgG (Fig 4D).…”