{"doi":"10.1016/j.mucimm.2024.06.001","title":"Lung influenza virus-specific memory CD4 T cell location and optimal cytokine production are dependent on interactions with lung antigen-presenting cells","abstract":"Influenza A virus (IAV) infection leads to the formation of mucosal memory CD4 T cells that can protect the host. An in-depth understanding of the signals that shape memory cell development is required for more effective vaccine design. We have examined the formation of memory CD4 T cells in the lung following IAV infection of mice, characterizing changes to the lung landscape and immune cell composition. IAV-specific CD4 T cells were found throughout the lung at both primary and memory time points. These cells were found near lung airways and in close contact with a range of immune cells including macrophages, dendritic cells, and B cells. Interactions between lung IAV-specific CD4 T cells and major histocompatibility complex (MHC)II+ cells during the primary immune response were important in shaping the subsequent memory pool. Treatment with an anti-MHCII blocking antibody increased the proportion of memory CD4 T cells found in lung airways but reduced interferon-γ expression by IAV-specific immunodominant memory CD4 T cells. The immunodominant CD4 T cells expressed higher levels of programmed death ligand 1 (PD1) than other IAV-specific CD4 T cells and PD1+ memory CD4 T cells were located further away from MHCII+ cells than their PD1-low counterparts. This distinction in location was lost in mice treated with anti-MHCII antibodies. These data suggest that sustained antigen presentation in the lung impacts the formation of memory CD4 T cells by regulating their cytokine production and location.","journal":"Mucosal Immunology","year":2024,"id":457779,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9563,"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":1083771,"name":"Julie C. Worrell","orcid":"0000-0001-7754-1364","position":1,"is_corresponding":false},{"id":1177569,"name":"Chiara Pirillo","orcid":"0000-0001-6467-4627","position":2,"is_corresponding":false},{"id":1283290,"name":"Euan Brennan","orcid":"0009-0008-0201-7216","position":3,"is_corresponding":false},{"id":1177990,"name":"Andreu Masdefiol Garriga","orcid":null,"position":4,"is_corresponding":false},{"id":225928,"name":"Joshua I. Gray","orcid":"0000-0003-2796-5470","position":5,"is_corresponding":false},{"id":1083769,"name":"Thomas Purnell","orcid":"0000-0002-9551-7947","position":6,"is_corresponding":false},{"id":240174,"name":"Edward W. Roberts","orcid":"0000-0002-8229-1715","position":7,"is_corresponding":false},{"id":457701,"name":"Megan K. L. MacLeod","orcid":"0000-0003-1843-8580","position":8,"is_corresponding":false},{"id":480889,"name":"Kerrie E Hargrave","orcid":"0000-0001-6015-4616","position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":null,"created_at":"2026-07-19T02:03:41.744499Z","pmid":"38851589","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":[]}