{"doi":"10.1101/2024.01.23.576505","title":"CD4+ and CD8+ T cells are required to prevent SARS-CoV-2 persistence in the nasal compartment","abstract":"ABSTRACT SARS-CoV-2 is the causative agent of COVID-19 and continues to pose a significant public health threat throughout the world. Following SARS-CoV-2 infection, virus-specific CD4+ and CD8+ T cells are rapidly generated to form effector and memory cells and persist in the blood for several months. However, the contribution of T cells in controlling SARS-CoV-2 infection within the respiratory tract are not well understood. Using C57BL/6 mice infected with a naturally occurring SARS-CoV-2 variant (B.1.351), we evaluated the role of T cells in the upper and lower respiratory tract. Following infection, 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 antibodies to deplete T cells prior to infection, we found that CD4+ and CD8+ T cells play distinct roles in the upper and lower respiratory tract. In the lungs, T cells play a minimal role in viral control with viral clearance occurring in the absence of both CD4+ and CD8+ T cells through 28 days post-infection. In the nasal compartment, depletion of both CD4+ and CD8+ T cells, but not individually, results in persistent and culturable virus replicating in the nasal compartment through 28 days post-infection. Using in situ hybridization, we found that SARS-CoV-2 infection persisted in the nasal epithelial layer of tandem CD4+ and CD8+ T cell-depleted mice. Sequence analysis of virus isolates from persistently infected mice revealed mutations spanning across the genome, including a 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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":487771,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9534,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1063514,"name":"Katherine Johnson","orcid":"0000-0002-9226-0672","position":1,"is_corresponding":false},{"id":106936,"name":"Abigail Vanderheiden","orcid":"0000-0003-1321-4510","position":2,"is_corresponding":false},{"id":369206,"name":"Elizabeth J. Elrod","orcid":"0000-0003-1236-5309","position":3,"is_corresponding":false},{"id":218085,"name":"Katharine Floyd","orcid":"0000-0002-0866-6961","position":4,"is_corresponding":false},{"id":409041,"name":"Elizabeth Geerling","orcid":"0000-0002-5104-499X","position":5,"is_corresponding":false},{"id":409039,"name":"E. Taylor Stone","orcid":"0000-0001-6742-1270","position":6,"is_corresponding":false},{"id":328827,"name":"Eduardo Salinas","orcid":"0000-0002-4490-9289","position":7,"is_corresponding":false},{"id":624749,"name":"Stephanie Banakis","orcid":null,"position":8,"is_corresponding":false},{"id":882454,"name":"Wei Wang","orcid":"0000-0001-7788-1895","position":9,"is_corresponding":false},{"id":1224414,"name":"Shruti Sathish","orcid":null,"position":10,"is_corresponding":false},{"id":106516,"name":"Swathi Shrihari","orcid":"0000-0002-8188-6936","position":11,"is_corresponding":false},{"id":329379,"name":"Meredith E. Davis-Gardner","orcid":"0000-0002-6133-3613","position":12,"is_corresponding":false},{"id":232939,"name":"Jacob E. Kohlmeier","orcid":"0000-0002-7209-6641","position":13,"is_corresponding":false},{"id":290891,"name":"Amelia K. Pinto","orcid":"0000-0002-7147-3978","position":14,"is_corresponding":false},{"id":230439,"name":"Robyn S. Klein","orcid":"0000-0003-0281-1352","position":15,"is_corresponding":false},{"id":227332,"name":"Arash Grakoui","orcid":"0000-0002-6002-7518","position":16,"is_corresponding":false},{"id":294797,"name":"Elodie Ghedin","orcid":"0000-0002-1515-725X","position":17,"is_corresponding":false},{"id":106937,"name":"Mehul S. Suthar","orcid":"0000-0002-2686-8380","position":18,"is_corresponding":false},{"id":1223837,"name":"Meenakshi Kar","orcid":"0000-0003-3332-811X","position":0,"is_corresponding":true}],"reference_count":80,"raw_metadata":null,"created_at":"2026-07-19T02:08:10.215754Z","pmid":"38410446","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}