{"doi":"10.1084/jem.20231193","title":"Precursor central memory versus effector cell fate and naïve CD4+ T cell heterogeneity","abstract":"Upon antigenic stimulation, naïve CD4+ T cells can give rise to phenotypically distinct effector T helper cells and long-lived memory T cells. We computationally reconstructed the in vivo trajectory of CD4+ T cell differentiation during a type I inflammatory immune response and identified two distinct differentiation paths for effector and precursor central memory T cells arising directly from naïve CD4+ T cells. Unexpectedly, our studies revealed heterogeneity among naïve CD4+ T cells, which are typically considered homogeneous save for their diverse T cell receptor usage. Specifically, a previously unappreciated population of naïve CD4+ T cells sensing environmental type I IFN exhibited distinct activation thresholds, suggesting that naïve CD4+ T cell differentiation potential may be influenced by environmental cues. This population was expanded in human viral infection and type I IFN response-lined autoimmunity. Understanding the relevance of naïve T cell heterogeneity to beneficial and maladaptive T cell responses may have therapeutic implications for adoptive T cell therapies in cancer immunotherapy and vaccination.","journal":"The Journal of Experimental Medicine","year":2024,"id":433336,"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":14,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9453,"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":1239071,"name":"Herman Gudjonson","orcid":null,"position":1,"is_corresponding":false},{"id":418097,"name":"Chrysothemis C. Brown","orcid":"0000-0002-5834-926X","position":2,"is_corresponding":false},{"id":16700,"name":"Samuel A. Rose","orcid":"0000-0001-9701-0050","position":3,"is_corresponding":false},{"id":240161,"name":"Roshan Sharma","orcid":"0000-0001-9886-009X","position":4,"is_corresponding":false},{"id":841667,"name":"Yoselin A. Paucar Iza","orcid":"0000-0003-2151-9058","position":5,"is_corresponding":false},{"id":1238605,"name":"Seunghee Hong","orcid":"0000-0002-0134-1195","position":6,"is_corresponding":false},{"id":322697,"name":"Saskia Hemmers","orcid":"0000-0002-5575-0509","position":7,"is_corresponding":false},{"id":218452,"name":"Michail Schizas","orcid":"0000-0002-9285-6951","position":8,"is_corresponding":false},{"id":145143,"name":"Zhong-Min Wang","orcid":null,"position":9,"is_corresponding":false},{"id":106727,"name":"Yuezhou Chen","orcid":"0000-0003-3453-1988","position":10,"is_corresponding":false},{"id":106756,"name":"Duane R. Wesemann","orcid":"0000-0002-6690-944X","position":11,"is_corresponding":false},{"id":106471,"name":"Virginia Pascual","orcid":"0000-0002-8806-8426","position":12,"is_corresponding":false},{"id":104368,"name":"Dana Pe’er","orcid":"0000-0002-9259-8817","position":13,"is_corresponding":false},{"id":90403,"name":"Alexander Y. Rudensky","orcid":"0000-0003-1280-2898","position":14,"is_corresponding":false},{"id":628327,"name":"Deeksha Deep","orcid":"0000-0003-4315-1354","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":null,"created_at":"2026-07-19T01:59:44.444627Z","pmid":"39321257","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":[]}