{"doi":"10.1101/2020.08.31.275842","title":"IL-4-induced hysteresis in naïve T cell activation","abstract":"Abstract Naïve T cells are generally considered to be a homogeneous population, but for their unique T cell receptors (TCRs). Naïve T cells are activated within a specific cytokine milieu upon interaction with antigen-presenting cells through cognate TCR::MHC-peptide interaction and co-stimulation. Here we demonstrate that naïve T cells are transcriptionally heterogeneous, and that the relative proportions of transcriptionally distinct naïve T cell subpopulations are modified by immune responses, such as during helminth infection. Not only are cognate naïve T cells activated during an immune response, but the cytokine produced - such as IL-4 during helminth infection - changes the transcriptome of bystander naïve T cells. Such changes in gene expression and population level heterogeneity in bystander naïve T cells result in altered responses to a concurrent immune challenge, for instance, hypo-responsiveness to vaccination. Thus, naïve T cell activation is not the result of a singular temporal event, but is characterized by hysteresis. Our studies suggest that antigen-agnostic, cytokine-dependent naïve T cell conditioning and resulting hysteresis is a mechanism that integrates input signals from concurrent infections for the regulation of the overall magnitude of the immune response.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":127289,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9489,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":575952,"name":"Yaqiu Wang","orcid":"0000-0002-6827-5495","position":1,"is_corresponding":false},{"id":520967,"name":"Dimitri de Kouchkovsky","orcid":"0000-0002-9609-3226","position":2,"is_corresponding":false},{"id":51180,"name":"Yong Kong","orcid":"0000-0002-2881-5274","position":3,"is_corresponding":false},{"id":495576,"name":"Malay Kumar Basu","orcid":"0000-0002-8008-4042","position":4,"is_corresponding":false},{"id":294262,"name":"Sourav Ghosh","orcid":"0000-0001-5990-8708","position":5,"is_corresponding":false},{"id":294261,"name":"Carla V. Rothlin","orcid":"0000-0002-5693-5572","position":6,"is_corresponding":false},{"id":575951,"name":"Alexandre P. Meli","orcid":"0000-0002-6199-3531","position":0,"is_corresponding":true}],"reference_count":37,"raw_metadata":null,"created_at":"2026-07-18T23:15:30.930746Z","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":[]}