CD4 <sup>+</sup> and CD8 <sup>+</sup> T cells are required to prevent SARS-CoV-2 persistence in the nasal compartment-Reference-Cited by-同舟云学术

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

Published:2024-08-23 Issue:34 Volume:10 Page:
ISSN:2375-2548
Container-title:Science Advances
language:en
Short-container-title:Sci. Adv.

Author:

Kar Meenakshi¹²³^ORCID,Johnson Katherine E. E.⁴^ORCID,Vanderheiden Abigail⁵⁶^ORCID,Elrod Elizabeth J.²³⁷^ORCID,Floyd Katharine¹²³^ORCID,Geerling Elizabeth⁸,Stone E. Taylor⁸^ORCID,Salinas Eduardo²³⁷,Banakis Stephanie⁴^ORCID,Wang Wei⁴^ORCID,Sathish Shruti⁴^ORCID,Shrihari Swathi¹²³^ORCID,Davis-Gardner Meredith E.¹²³^ORCID,Kohlmeier Jacob⁹^ORCID,Pinto Amelia⁸^ORCID,Klein Robyn¹⁰¹¹,Grakoui Arash²³⁷^ORCID,Ghedin Elodie⁴^ORCID,Suthar Mehul S.¹²³⁹^ORCID

Affiliation:

1. Center for Childhood Infections and Vaccines of Children’s Healthcare of Atlanta, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.

2. Emory Vaccine Center, Emory University, Atlanta, GA, USA.

3. Emory National Primate Research Center, Atlanta, GA, USA.

4. Systems Genomics Section, Laboratory of Parasitic Diseases, DIR, NIAID, NIH, Bethesda, MD, USA.

5. Center for Neuroimmunology and Neuroinfectious Diseases, Washington University School of Medicine, St. Louis, MO, USA.

6. Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.

7. Department of Medicine, Emory University School of Medicine, Emory University, Atlanta, GA, USA.

8. Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, Saint Louis, MO, USA.

9. Department of Microbiology and Immunology, Emory University, Atlanta, GA, USA.

10. Schulich School of Medicine and Dentistry, Department of Microbiology and Immunology, Western University, London, Ontario, Canada.

11. Schulich School of Medicine and Dentistry, Western Institute of Neuroscience, Western University, London, Ontario, Canada.

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.

Publisher

American Association for the Advancement of Science (AAAS)

Link

https://www.science.org/doi/pdf/10.1126/sciadv.adp2636

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