{"doi":"10.3389/fbioe.2025.1587080","title":"Lung-resident SARS-CoV-2 peptide-specific immune responses in perfused 3D human lung explant models","abstract":"Introduction Multi-specific and long-lasting T-cell immunity has been recognized to indicate long-term protection against pathogens, including the novel coronavirus, SARS-CoV-2, which is the causative agent of the COVID-19 pandemic. Functional significance of peripheral memory T cells in individuals recovered from COVID-19 (COVID-19 + ) is beginning to be appreciated; however, the role of lung tissue-resident memory (lung TRM) T cells in SARS-CoV-2 infection is still being investigated. This is, in part, due to the lack of preclinical tissue models available to follow the convalescence period. Methods Here, we utilize a perfused three-dimensional (3D) human lung-tissue model and show pre-existing local T-cell immunity against SARS-CoV-2 proteins in lung tissues. Results We report ex vivo maintenance of functional multi-specific IFN-γ-secreting lung TRM T cells in COVID-19 + and their induction in lung tissues of vaccinated COVID-19 + subjects. Importantly, we identify SARS-CoV-2 peptide-responding memory B cells and IgA + plasma cells in ex vivo cultured lung tissues of COVID-19 + . Furthermore, lung tissue IgA levels were increased in COVID-19 + and responded to peptide stimulation. Discussion In our study, we highlight the importance of utilization of human lung-tissue models to understand the local antiviral immune response in the lung to protect against SARS-CoV-2 infection.","journal":"Frontiers in Bioengineering and Biotechnology","year":2025,"id":545222,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9545,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":756509,"name":"Anthony M. Wood","orcid":null,"position":1,"is_corresponding":false},{"id":809414,"name":"Christopher S. Simmons","orcid":"0009-0004-4675-8324","position":2,"is_corresponding":false},{"id":809415,"name":"Rabisa Khan","orcid":"0009-0005-6511-0926","position":3,"is_corresponding":false},{"id":809416,"name":"Saad Khan","orcid":"0000-0002-0491-8180","position":4,"is_corresponding":false},{"id":809417,"name":"Yong Wang","orcid":"0000-0002-0821-6549","position":5,"is_corresponding":false},{"id":939975,"name":"Rekha Ramachandran","orcid":"0009-0002-0184-0426","position":6,"is_corresponding":false},{"id":455991,"name":"Joel L. Berry","orcid":null,"position":7,"is_corresponding":false},{"id":315214,"name":"Mohammad Athar","orcid":"0000-0002-4728-2530","position":8,"is_corresponding":false},{"id":338889,"name":"James A. Mobley","orcid":"0000-0002-3229-7975","position":9,"is_corresponding":false},{"id":442450,"name":"Young-il Kim","orcid":"0000-0001-6806-4551","position":10,"is_corresponding":false},{"id":228870,"name":"Victor J. Thannickal","orcid":"0000-0003-4266-8677","position":11,"is_corresponding":false},{"id":569741,"name":"Kevin S. Harrod","orcid":"0000-0003-0780-9470","position":12,"is_corresponding":false},{"id":1396132,"name":"James Donahue","orcid":null,"position":13,"is_corresponding":false},{"id":228869,"name":"Jessy S. Deshane","orcid":"0000-0002-6761-5662","position":14,"is_corresponding":false},{"id":755727,"name":"Kayla F. Goliwas","orcid":"0000-0002-6930-6636","position":0,"is_corresponding":true}],"reference_count":75,"raw_metadata":null,"created_at":"2026-07-19T02:53:23.001995Z","pmid":"40698364","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":[]}