{"doi":"10.1126/sciadv.adq6618","title":"Naturally arising memory-phenotype CD4 <sup>+</sup> T lymphocytes contain an undifferentiated population that can generate T <sub>H</sub> 1, T <sub>H</sub> 17, and T <sub>reg</sub> cells","abstract":"Memory-phenotype (MP) CD4 + T lymphocytes develop from naïve cells via self-recognition at homeostasis. While previous studies defined MP cells as a heterogeneous population that comprises T helper 1 (T H 1)/17–like subsets, functional significance of the T-bet − Rorγt − subpopulation remains unknown. Here we show that MP lymphocytes as a whole population can differentiate into T H 1/17/regulatory T (T reg ) cells to mediate mild and persistent inflammation in lymphopenic environments, whereas naïve cells exhibit strong, T H 1-dominated responses. Moreover, we demonstrate that MP lymphocytes comprise not only T H 1/17-differentiated subsets but a polyclonal, transcriptomically immature “undifferentiated” subpopulation at homeostasis. Furthermore, our data argue that while the T-bet + Rorγt − MP subset is terminally T H 1-differentiated, its undifferentiated counterpart retains the capacity to rapidly proliferate to differentiate into T H 1/17/T reg cells, with the latter response tonically constrained by preexisting T reg cells. Together, our results identify undifferentiated MP CD4 + T lymphocytes as a unique precursor that has a diverse differentiation potential to generate T H 1/17/T reg cells to contribute to pathogenesis of inflammation.","journal":"Science Advances","year":2024,"id":449677,"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":0.951,"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":662068,"name":"Jing Li","orcid":"0000-0001-8375-7890","position":1,"is_corresponding":false},{"id":1269964,"name":"Keita Koinuma","orcid":null,"position":2,"is_corresponding":false},{"id":1269472,"name":"Ziying Yang","orcid":"0000-0002-9606-4900","position":3,"is_corresponding":false},{"id":1269473,"name":"Hye Jin Yoon","orcid":"0009-0007-8705-1677","position":4,"is_corresponding":false},{"id":506217,"name":"Jaeu Yi","orcid":"0000-0003-4907-3924","position":5,"is_corresponding":false},{"id":313437,"name":"Hiroyuki Nagashima","orcid":"0000-0001-8405-6746","position":6,"is_corresponding":false},{"id":1269965,"name":"Minami Ishii","orcid":null,"position":7,"is_corresponding":false},{"id":1081751,"name":"Feng Gao","orcid":"0009-0006-5629-8602","position":8,"is_corresponding":false},{"id":1269474,"name":"Kosuke Sato","orcid":"0000-0001-8754-5975","position":9,"is_corresponding":false},{"id":1269475,"name":"Shunichi Tayama","orcid":"0009-0000-9568-2718","position":10,"is_corresponding":false},{"id":801964,"name":"Hideo Harigae","orcid":"0000-0003-4849-7442","position":11,"is_corresponding":false},{"id":608927,"name":"Yoichiro Iwakura","orcid":"0000-0002-9934-5775","position":12,"is_corresponding":false},{"id":506219,"name":"Naoto Ishii","orcid":"0000-0002-0549-8245","position":13,"is_corresponding":false},{"id":330710,"name":"Alan Sher","orcid":"0000-0001-7053-2895","position":14,"is_corresponding":false},{"id":244836,"name":"Kazuyoshi Ishigaki","orcid":"0000-0003-2881-0657","position":15,"is_corresponding":false},{"id":231485,"name":"Jinfang Zhu","orcid":"0000-0002-0117-4745","position":16,"is_corresponding":false},{"id":506220,"name":"Kwang Soon Kim","orcid":"0000-0002-6250-1068","position":17,"is_corresponding":false},{"id":506216,"name":"Takeshi Kawabe","orcid":"0000-0001-7173-4472","position":18,"is_corresponding":false},{"id":506218,"name":"Akihisa Kawajiri","orcid":"0000-0002-5989-7786","position":0,"is_corresponding":true}],"reference_count":89,"raw_metadata":null,"created_at":"2026-07-19T02:02:20.585759Z","pmid":"39630890","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":[]}