{"doi":"10.1016/j.immuni.2023.12.006","title":"Reversible, tunable epigenetic silencing of TCF1 generates flexibility in the T cell memory decision","abstract":"The immune system encodes information about the severity of a pathogenic threat in the quantity and type of memory cells it forms. This encoding emerges from lymphocyte decisions to maintain or lose self-renewal and memory potential during a challenge. By tracking CD8+ T cells at the single-cell and clonal lineage level using time-resolved transcriptomics, quantitative live imaging, and an acute infection model, we find that T cells will maintain or lose memory potential early after antigen recognition. However, following pathogen clearance, T cells may regain memory potential if initially lost. Mechanistically, this flexibility is implemented by a stochastic cis-epigenetic switch that tunably and reversibly silences the memory regulator, TCF1, in response to stimulation. Mathematical modeling shows how this flexibility allows memory T cell numbers to scale robustly with pathogen virulence and immune response magnitudes. We propose that flexibility and stochasticity in cellular decisions ensure optimal immune responses against diverse threats.","journal":"Immunity","year":2024,"id":418307,"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":52,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9411,"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":686098,"name":"Elisa C. Clark","orcid":"0000-0003-4267-7215","position":1,"is_corresponding":false},{"id":865059,"name":"Rajesh M. Valanparambil","orcid":"0000-0002-0888-7246","position":2,"is_corresponding":false},{"id":989606,"name":"Obinna Ukogu","orcid":"0000-0002-6170-9035","position":3,"is_corresponding":false},{"id":263690,"name":"Wei Yang","orcid":"0000-0002-3591-2195","position":4,"is_corresponding":false},{"id":36581,"name":"Riza M. Daza","orcid":"0000-0003-1635-8675","position":5,"is_corresponding":false},{"id":690877,"name":"Kenneth K.H. Ng","orcid":"0000-0003-4218-8841","position":6,"is_corresponding":false},{"id":990014,"name":"Jumana Fathima","orcid":null,"position":7,"is_corresponding":false},{"id":990015,"name":"Allan L. Wang","orcid":null,"position":8,"is_corresponding":false},{"id":253106,"name":"Judong Lee","orcid":null,"position":9,"is_corresponding":false},{"id":176771,"name":"Tahseen H. Nasti","orcid":"0000-0002-5650-1563","position":10,"is_corresponding":false},{"id":471420,"name":"Avinash Bhandoola","orcid":"0000-0002-4657-8372","position":11,"is_corresponding":false},{"id":292836,"name":"Armita Nourmohammad","orcid":"0000-0002-6245-3553","position":12,"is_corresponding":false},{"id":226172,"name":"Rafi Ahmed","orcid":"0000-0002-9591-2621","position":13,"is_corresponding":false},{"id":36510,"name":"Jay Shendure","orcid":"0000-0002-1516-1865","position":14,"is_corresponding":false},{"id":94703,"name":"Junyue Cao","orcid":"0000-0003-4097-489X","position":15,"is_corresponding":false},{"id":478763,"name":"Hao Yuan Kueh","orcid":"0000-0001-6272-6673","position":16,"is_corresponding":false},{"id":71119,"name":"Kathleen Abadie","orcid":"0000-0003-2021-7365","position":0,"is_corresponding":true}],"reference_count":86,"raw_metadata":null,"created_at":"2026-07-19T01:57:02.483590Z","pmid":"38301652","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":[]}