{"doi":"10.1002/eji.200425957","title":"Human T helper (Th) cell lineage commitment is not directly linked to the secretion of IFN‐γ or IL‐4: Characterization of Th cells isolated by FACS based on IFN‐γ and IL‐4 secretion","abstract":"<jats:title>Abstract</jats:title><jats:p>Upon activation <jats:italic>in vitro</jats:italic>, only a fraction of the bulk human T helper cell cultures secret the hallmark Th1/2 cytokines (IFN‐γ for Th1 and IL‐4 for Th2, respectively). It is uncertain whether these IFN‐γ<jats:sup>–</jats:sup>/IL‐4<jats:sup>–</jats:sup> cells are differentiated Th1 or Th2 cells. Here, we have characterized live IFN‐γ<jats:sup>+</jats:sup>, IL‐4<jats:sup>+</jats:sup> and IFN‐γ<jats:sup>–</jats:sup>/IL‐4<jats:sup>–</jats:sup> cells isolated from Th cell cultures treated under Th1 or Th2 polarizing conditions by employing affinity matrix capture technology. RNA samples from the sorted cells were analyzed by real time RT‐PCR and microarrays. The double negative cells from either Th1 or Th2 cultures expressed lower levels of Th1/Th2 marker cytokine genes (<jats:italic>IFNγ, IL4</jats:italic>, and <jats:italic>IL5</jats:italic>). However, they were comparable with the IFN‐γ<jats:sup>+</jats:sup> or IL‐4<jats:sup>+</jats:sup> cells in the expression levels of other Th1/Th2 marker genes (<jats:italic>GATA3, Tbet</jats:italic>, and <jats:italic>IL12R<jats:sub>β</jats:sub>2</jats:italic>). Most importantly, these double negative cells were already committed in their Th1/Th2 lineages. Gene expression profiling analysis showed that very few previously identified Th1/Th2 marker genes were differentially expressed between the IFN‐γ or IL‐4 producers and the non‐producers, further underscoring the similarity between these two groups.</jats:p>","journal":"European Journal of Immunology","year":2005,"id":665287,"datarank":0.4887144807032224,"base_score":3.258096538021482,"endowment":3.258096538021482,"self_citation_contribution":0.4887144807032224,"citation_network_contribution":0.0,"self_endowment_contribution":0.4887144807032224,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":25,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":613762,"name":"Yangde Chen","orcid":"0000-0002-1191-2502","position":1,"is_corresponding":false},{"id":1737254,"name":"Sefik Alkan","orcid":null,"position":2,"is_corresponding":false},{"id":1737255,"name":"Arun Subramaniam","orcid":null,"position":3,"is_corresponding":false},{"id":1600697,"name":"Fan Long","orcid":null,"position":4,"is_corresponding":false},{"id":334681,"name":"Hong Liu","orcid":"0000-0003-3611-7131","position":5,"is_corresponding":false},{"id":1737256,"name":"Rong Diao","orcid":null,"position":6,"is_corresponding":false},{"id":1737257,"name":"Thomas Delohery","orcid":null,"position":7,"is_corresponding":false},{"id":815403,"name":"Jason McCormick","orcid":"0009-0007-0052-4727","position":8,"is_corresponding":false},{"id":451156,"name":"Rong Chen","orcid":"0000-0003-1298-9381","position":9,"is_corresponding":false},{"id":1737258,"name":"Donghui Ni","orcid":null,"position":10,"is_corresponding":false},{"id":1737259,"name":"Paul S. Wright","orcid":null,"position":11,"is_corresponding":false},{"id":294622,"name":"Xin Zhang","orcid":"0000-0002-5941-3921","position":12,"is_corresponding":false},{"id":1737260,"name":"Steve Busch","orcid":null,"position":13,"is_corresponding":false},{"id":1737261,"name":"Asher Zilberstein","orcid":null,"position":14,"is_corresponding":false},{"id":1737251,"name":"Wuxiong Cao","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Human T helper (Th) cell lineage commitment is not directly linked to the secretion of IFN‐γ or IL‐4: Characterization of Th cells isolated by FACS based on IFN‐γ and IL‐4 secretion","abstract":"<jats:title>Abstract</jats:title><jats:p>Upon activation <jats:italic>in vitro</jats:italic>, only a fraction of the bulk human T helper cell cultures secret the hallmark Th1/2 cytokines (IFN‐γ for Th1 and IL‐4 for Th2, respectively). It is uncertain whether these IFN‐γ<jats:sup>–</jats:sup>/IL‐4<jats:sup>–</jats:sup> cells are differentiated Th1 or Th2 cells. Here, we have characterized live IFN‐γ<jats:sup>+</jats:sup>, IL‐4<jats:sup>+</jats:sup> and IFN‐γ<jats:sup>–</jats:sup>/IL‐4<jats:sup>–</jats:sup> cells isolated from Th cell cultures treated under Th1 or Th2 polarizing conditions by employing affinity matrix capture technology. RNA samples from the sorted cells were analyzed by real time RT‐PCR and microarrays. The double negative cells from either Th1 or Th2 cultures expressed lower levels of Th1/Th2 marker cytokine genes (<jats:italic>IFNγ, IL4</jats:italic>, and <jats:italic>IL5</jats:italic>). However, they were comparable with the IFN‐γ<jats:sup>+</jats:sup> or IL‐4<jats:sup>+</jats:sup> cells in the expression levels of other Th1/Th2 marker genes (<jats:italic>GATA3, Tbet</jats:italic>, and <jats:italic>IL12R<jats:sub>β</jats:sub>2</jats:italic>). Most importantly, these double negative cells were already committed in their Th1/Th2 lineages. Gene expression profiling analysis showed that very few previously identified Th1/Th2 marker genes were differentially expressed between the IFN‐γ or IL‐4 producers and the non‐producers, further underscoring the similarity between these two groups.</jats:p>","is_dataset_classified":null,"base_score":3.258096538021482,"endowment":3.258096538021482,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"16106470","pmcid":null,"openalex_id":"https://openalex.org/W1965092495","authors":[],"funders":[],"total_grants":0,"fwci":0.9274,"citation_percentile":0.72293355,"influential_citations":0,"citation_trend":[{"year":2012,"count":2},{"year":2013,"count":2},{"year":2014,"count":1},{"year":2015,"count":1},{"year":2018,"count":1},{"year":2019,"count":1},{"year":2020,"count":1},{"year":2022,"count":2},{"year":2023,"count":1},{"year":2024,"count":1},{"year":2026,"count":1}],"oa_status":"bronze","license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/eji.200425957","host_type":"journal"},{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/eji.200425957","host_type":"publisher"},{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Feji.200425957","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1002/eji.200425957","host_type":"publisher"},{"url":"https://doi.org/10.1002/eji.200425957","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/16106470","host_type":"repository"}],"fields_of_study":["T-cell and B-cell Immunology","Immune Cell Function and Interaction","Immunotherapy and Immune Responses","Cell Differentiation","Cell Lineage","DNA-Binding Proteins","Flow Cytometry","GATA3 Transcription Factor","Gene Expression","Genetic Markers","Humans","Interferon-gamma","Interleukin-4","RNA","Reverse Transcriptase Polymerase Chain Reaction","Th1 Cells","Th2 Cells","Trans-Activators"],"mesh_terms":["Cell Differentiation","DNA-Binding Proteins","Flow Cytometry","Genetic Markers","Humans","Interferon-gamma","RNA","Trans-Activators","Interleukin-4","Gene Expression","Th1 Cells","Th2 Cells","Cell Lineage","Reverse Transcriptase Polymerase Chain Reaction","GATA3 Transcription Factor"],"keywords":["Biology","GATA3","Interleukin 4","T helper cell","Gene","Molecular biology","In vitro","Gene expression profiling","T cell","Cytokine","Gene expression","Immunology","Transcription factor","Immune system","Genetics"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Partnerships for the goals"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-13T08:10:44.519922Z","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":[]}