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

J Exp Med. 2021 Apr 5;218(4):e20202187. doi: 10.1084/jem.20202187.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme 2 / genetics
  • Angiotensin-Converting Enzyme 2 / metabolism
  • Animals
  • Antibodies, Neutralizing / blood
  • CD4-Positive T-Lymphocytes / virology
  • CD8-Positive T-Lymphocytes / virology
  • COVID-19 / immunology*
  • Chlorocebus aethiops
  • Cross Reactions
  • Epitope Mapping
  • Epitopes, T-Lymphocyte / immunology*
  • Host-Pathogen Interactions / physiology*
  • Interferon Type I / immunology
  • Interferon Type I / metabolism
  • 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*
  • Vero Cells

Substances

  • Antibodies, Neutralizing
  • Epitopes, T-Lymphocyte
  • Interferon Type I
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2