{"doi":"10.1101/2022.08.14.503916","title":"Plasticity and lineage commitment of individual Th1 cells are determined by stable T-bet expression quantities","abstract":"SUMMARY T helper 1 (Th1) cell identity is defined by the expression of the lineage-defining transcription factor T-bet. Here, we examine the influence of T-bet expression heterogeneity on subset plasticity by leveraging cell sorting of distinct in vivo -differentiated Th1 cells based on their quantitative expression of T-bet and interferon-γ. Heterogeneous T-bet expression states were regulated by virus-induced type-I interferons and were stably maintained even after secondary viral infection. Exposed to Th2-polarizing conditions, the sorted subpopulations exhibited graded levels of plasticity: T-bet quantities were inversely correlated with the ability to express the Th2 lineage-specifying transcription factor GATA-3 and Th2 cytokines. Reprogramed Th1 cells acquired graded, but stable mixed Th1+2 phenotypes with a hybrid epigenetic landscape. Continuous presence of T-bet in differentiated Th1 cells was essential to ensure Th1 cell stability. Thus, innate cytokine signals regulate Th1 cell plasticity via an individual cell-intrinsic rheostat to enable T cell subset adaptation to subsequent challenges. HIGHLIGHTS Type-I interferons triggered by infection determine T-bet expression states in Th1 cells T-bet and IFN-γ expression states indicate the plasticity of individual Th1 cells Individual T-bet expression states and plasticity persist after secondary infection Reprogramming yields stable Th1+2 phenotypes and a mixed epigenetic landscape","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":301692,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.96,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":993140,"name":"Caroline Peine","orcid":"0000-0001-6267-3452","position":1,"is_corresponding":false},{"id":993141,"name":"Dominik Niesen","orcid":"0000-0003-3204-123X","position":2,"is_corresponding":false},{"id":993741,"name":"Isabel Panse","orcid":null,"position":3,"is_corresponding":false},{"id":993142,"name":"Yevhen Vainshtein","orcid":"0000-0001-7944-8892","position":4,"is_corresponding":false},{"id":993742,"name":"Christoph Kommer","orcid":null,"position":5,"is_corresponding":false},{"id":817321,"name":"Qin Zhang","orcid":"0009-0009-5451-4051","position":6,"is_corresponding":false},{"id":993143,"name":"Tobias M. Brunner","orcid":"0000-0002-5279-2391","position":7,"is_corresponding":false},{"id":993743,"name":"Anja Fröhlich","orcid":null,"position":9,"is_corresponding":false},{"id":58477,"name":"Naveed Ishaque","orcid":"0000-0002-8426-901X","position":10,"is_corresponding":false},{"id":993144,"name":"Roman Marek","orcid":"0000-0002-5267-2787","position":11,"is_corresponding":false},{"id":231485,"name":"Jinfang Zhu","orcid":"0000-0002-0117-4745","position":12,"is_corresponding":false},{"id":84771,"name":"Thomas Höfer","orcid":"0000-0003-3560-8780","position":13,"is_corresponding":false},{"id":993145,"name":"Max Löhning","orcid":"0000-0001-6382-7281","position":14,"is_corresponding":false},{"id":618096,"name":"Ahmed N. Hegazy","orcid":"0000-0002-2946-8251","position":0,"is_corresponding":true}],"reference_count":43,"raw_metadata":null,"created_at":"2026-07-19T00:32:06.309890Z","pmid":null,"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":[]}