CD4+ and CD8+ T cells are required to prevent SARS-CoV-2 persistence in the nasal compartment

Sci Adv. 2024 Aug 23;10(34):eadp2636. doi: 10.1126/sciadv.adp2636. Epub 2024 Aug 23.

Abstract

SARS-CoV-2 infection induces the generation of virus-specific CD4+ and CD8+ effector and memory T cells. However, the contribution of T cells in controlling SARS-CoV-2 during infection is not well understood. Following infection of C57BL/6 mice, SARS-CoV-2-specific CD4+ and CD8+ T cells are recruited to the respiratory tract, and a vast proportion secrete the cytotoxic molecule granzyme B. Using depleting antibodies, we found that T cells within the lungs play a minimal role in viral control, and viral clearance occurs in the absence of both CD4+ and CD8+ T cells through 28 days postinfection. In the nasal compartment, depletion of both CD4+ and CD8+ T cells, but not individually, results in persistent, culturable virus replicating in the nasal epithelial layer through 28 days postinfection. Viral sequencing analysis revealed adapted mutations across the SARS-CoV-2 genome, including a large deletion in ORF6. Overall, our findings highlight the importance of T cells in controlling virus replication within the respiratory tract during SARS-CoV-2 infection.

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes* / immunology
  • CD4-Positive T-Lymphocytes* / metabolism
  • CD4-Positive T-Lymphocytes* / virology
  • CD8-Positive T-Lymphocytes* / immunology
  • CD8-Positive T-Lymphocytes* / metabolism
  • COVID-19* / immunology
  • COVID-19* / prevention & control
  • COVID-19* / virology
  • Female
  • Granzymes / metabolism
  • Humans
  • Lung / immunology
  • Lung / virology
  • Mice
  • Mice, Inbred C57BL*
  • Nasal Mucosa / immunology
  • Nasal Mucosa / metabolism
  • Nasal Mucosa / virology
  • SARS-CoV-2* / immunology
  • SARS-CoV-2* / physiology
  • Virus Replication*

Substances

  • Granzymes