tetano
Editor, Senior Moderator
Sci Adv
. 2024 Aug 23;10(34):eadp2636.
doi: 10.1126/sciadv.adp2636. Epub 2024 Aug 23. CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] T cells are required to prevent SARS-CoV-2 persistence in the nasal compartment
Meenakshi Kar[SUP] 1 2 3 [/SUP], Katherine E E Johnson[SUP] 4 [/SUP], Abigail Vanderheiden[SUP] 5 6 [/SUP], Elizabeth J Elrod[SUP] 2 3 7 [/SUP], Katharine Floyd[SUP] 1 2 3 [/SUP], Elizabeth Geerling[SUP] 8 [/SUP], E Taylor Stone[SUP] 8 [/SUP], Eduardo Salinas[SUP] 2 3 7 [/SUP], Stephanie Banakis[SUP] 4 [/SUP], Wei Wang[SUP] 4 [/SUP], Shruti Sathish[SUP] 4 [/SUP], Swathi Shrihari[SUP] 1 2 3 [/SUP], Meredith E Davis-Gardner[SUP] 1 2 3 [/SUP], Jacob Kohlmeier[SUP] 9 [/SUP], Amelia Pinto[SUP] 8 [/SUP], Robyn Klein[SUP] 10 11 [/SUP], Arash Grakoui[SUP] 2 3 7 [/SUP], Elodie Ghedin[SUP] 4 [/SUP], Mehul S Suthar[SUP] 1 2 3 9 [/SUP]
Affiliations
SARS-CoV-2 infection induces the generation of virus-specific CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] 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[SUP]+[/SUP] and CD8[SUP]+[/SUP] 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[SUP]+[/SUP] and CD8[SUP]+[/SUP] T cells through 28 days postinfection. In the nasal compartment, depletion of both CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] 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.
. 2024 Aug 23;10(34):eadp2636.
doi: 10.1126/sciadv.adp2636. Epub 2024 Aug 23. CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] T cells are required to prevent SARS-CoV-2 persistence in the nasal compartment
Meenakshi Kar[SUP] 1 2 3 [/SUP], Katherine E E Johnson[SUP] 4 [/SUP], Abigail Vanderheiden[SUP] 5 6 [/SUP], Elizabeth J Elrod[SUP] 2 3 7 [/SUP], Katharine Floyd[SUP] 1 2 3 [/SUP], Elizabeth Geerling[SUP] 8 [/SUP], E Taylor Stone[SUP] 8 [/SUP], Eduardo Salinas[SUP] 2 3 7 [/SUP], Stephanie Banakis[SUP] 4 [/SUP], Wei Wang[SUP] 4 [/SUP], Shruti Sathish[SUP] 4 [/SUP], Swathi Shrihari[SUP] 1 2 3 [/SUP], Meredith E Davis-Gardner[SUP] 1 2 3 [/SUP], Jacob Kohlmeier[SUP] 9 [/SUP], Amelia Pinto[SUP] 8 [/SUP], Robyn Klein[SUP] 10 11 [/SUP], Arash Grakoui[SUP] 2 3 7 [/SUP], Elodie Ghedin[SUP] 4 [/SUP], Mehul S Suthar[SUP] 1 2 3 9 [/SUP]
Affiliations
- PMID: 39178263
- PMCID: PMC11343035
- DOI: 10.1126/sciadv.adp2636
SARS-CoV-2 infection induces the generation of virus-specific CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] 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[SUP]+[/SUP] and CD8[SUP]+[/SUP] 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[SUP]+[/SUP] and CD8[SUP]+[/SUP] T cells through 28 days postinfection. In the nasal compartment, depletion of both CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] 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.