{"doi":"10.1371/journal.ppat.1009709","title":"Transgenic expression of a T cell epitope in Strongyloides ratti reveals that helminth-specific CD4+ T cells constitute both Th2 and Treg populations","abstract":"Helminths are distinct from microbial pathogens in both size and complexity, and are the likely evolutionary driving force for type 2 immunity. CD4+ helper T cells can both coordinate worm clearance and prevent immunopathology, but issues of T cell antigen specificity in the context of helminth-induced Th2 and T regulatory cell (Treg) responses have not been addressed. Herein, we generated a novel transgenic line of the gastrointestinal nematode Strongyloides ratti expressing the immunodominant CD4+ T cell epitope 2W1S as a fusion protein with green fluorescent protein (GFP) and FLAG peptide in order to track and study helminth-specific CD4+ T cells. C57BL/6 mice infected with this stable transgenic line (termed Hulk) underwent a dose-dependent expansion of activated CD44hiCD11ahi 2W1S-specific CD4+ T cells, preferentially in the lung parenchyma. Transcriptional profiling of 2W1S-specific CD4+ T cells isolated from mice infected with either Hulk or the enteric bacterial pathogen Salmonella expressing 2W1S revealed that pathogen context exerted a dominant influence over CD4+ T cell phenotype. Interestingly, Hulk-elicited 2W1S-specific CD4+ T cells exhibited both Th2 and Treg phenotypes and expressed high levels of the EGFR ligand amphiregulin, which differed greatly from the phenotype of 2W1S-specific CD4+ T cells elicited by 2W1S-expressing Salmonella. While immunization with 2W1S peptide did not enhance clearance of Hulk infection, immunization did increase total amphiregulin production as well as the number of amphiregulin-expressing CD3+ cells in the lung following Hulk infection. Altogether, this new model system elucidates effector as well as immunosuppressive and wound reparative roles of helminth-specific CD4+ T cells. This report establishes a new resource for studying the nature and function of helminth-specific T cells.","journal":"PLoS Pathogens","year":2021,"id":190140,"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":0.9571,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":753669,"name":"Yun Wei","orcid":"0000-0002-5404-619X","position":1,"is_corresponding":false},{"id":726478,"name":"Xinshe Li","orcid":null,"position":2,"is_corresponding":false},{"id":264130,"name":"Annabel A. Ferguson","orcid":"0000-0002-9691-7184","position":3,"is_corresponding":false},{"id":264125,"name":"Li‐Yin Hung","orcid":"0000-0001-7623-1946","position":4,"is_corresponding":false},{"id":264128,"name":"Christopher Pastore","orcid":"0000-0002-1002-6138","position":5,"is_corresponding":false},{"id":340245,"name":"Jonathan Kurtz","orcid":"0000-0001-9360-4433","position":6,"is_corresponding":false},{"id":304514,"name":"James B. McLachlan","orcid":"0000-0001-7741-391X","position":7,"is_corresponding":false},{"id":322395,"name":"Thomas J. Nolan","orcid":"0000-0002-6860-7947","position":8,"is_corresponding":false},{"id":473115,"name":"James B. Lok","orcid":"0000-0002-7611-8211","position":9,"is_corresponding":false},{"id":264138,"name":"De’Broski R. Herbert","orcid":"0000-0002-2449-5365","position":10,"is_corresponding":false},{"id":264131,"name":"Bonnie Douglas","orcid":"0000-0002-1039-7158","position":0,"is_corresponding":true}],"reference_count":69,"raw_metadata":null,"created_at":"2026-07-18T23:49:22.671571Z","pmid":"34237106","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":[]}