{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T10:13:14Z","timestamp":1792663994619,"version":"4.5.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1009709","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,7,20]],"date-time":"2021-07-20T00:00:00Z","timestamp":1626739200000}}],"reference-count":68,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2021,7,8]],"date-time":"2021-07-08T00:00:00Z","timestamp":1625702400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["U01-AI125940"],"award-info":[{"award-number":["U01-AI125940"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R21-AI-144572"],"award-info":[{"award-number":["R21-AI-144572"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000861","name":"Burroughs Wellcome Fund","doi-asserted-by":"publisher","award":["1013573.01"],"award-info":[{"award-number":["1013573.01"]}],"id":[{"id":"10.13039\/100000861","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01-AI-103343"],"award-info":[{"award-number":["R01-AI-103343"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    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\n                    <jats:italic>Strongyloides ratti<\/jats:italic>\n                    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\n                    <jats:italic>Hulk<\/jats:italic>\n                    ) underwent a dose-dependent expansion of activated CD44\n                    <jats:sup>hi<\/jats:sup>\n                    CD11a\n                    <jats:sup>hi<\/jats:sup>\n                    2W1S-specific CD4+ T cells, preferentially in the lung parenchyma. Transcriptional profiling of 2W1S-specific CD4+ T cells isolated from mice infected with either\n                    <jats:italic>Hulk<\/jats:italic>\n                    or the enteric bacterial pathogen\n                    <jats:italic>Salmonella<\/jats:italic>\n                    expressing 2W1S revealed that pathogen context exerted a dominant influence over CD4+ T cell phenotype. Interestingly,\n                    <jats:italic>Hulk<\/jats:italic>\n                    -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\n                    <jats:italic>Salmonella<\/jats:italic>\n                    . While immunization with 2W1S peptide did not enhance clearance of\n                    <jats:italic>Hulk<\/jats:italic>\n                    infection, immunization did increase total amphiregulin production as well as the number of amphiregulin-expressing CD3+ cells in the lung following\n                    <jats:italic>Hulk<\/jats:italic>\n                    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.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1009709","type":"journal-article","created":{"date-parts":[[2021,7,8]],"date-time":"2021-07-08T13:35:35Z","timestamp":1625751335000},"page":"e1009709","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":15,"title":["Transgenic expression of a T cell epitope in Strongyloides ratti reveals that helminth-specific CD4+ T cells constitute both Th2 and Treg populations"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1039-7158","authenticated-orcid":true,"given":"Bonnie","family":"Douglas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5404-619X","authenticated-orcid":true,"given":"Yun","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinshe","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annabel","family":"Ferguson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7623-1946","authenticated-orcid":true,"given":"Li-Yin","family":"Hung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1002-6138","authenticated-orcid":true,"given":"Christopher","family":"Pastore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9360-4433","authenticated-orcid":true,"given":"Jonathan R","family":"Kurtz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James B.","family":"McLachlan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6860-7947","authenticated-orcid":true,"given":"Thomas J.","family":"Nolan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Lok","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2449-5365","authenticated-orcid":true,"given":"De\u2019Broski R.","family":"Herbert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,7,8]]},"reference":[{"issue":"4","key":"ppat.1009709.ref001","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1172\/JCI34261","article-title":"Helminth infections: the great neglected tropical diseases","volume":"118","author":"PJ Hotez","year":"2008","journal-title":"J Clin Invest"},{"issue":"5","key":"ppat.1009709.ref002","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1097\/QCO.0000000000000395","article-title":"Prospects for elimination of soil-transmitted helminths","volume":"30","author":"KH \u00c1sbj\u00f6rnsd\u00f3ttir","year":"2017","journal-title":"Curr Opin Infect Dis.Oct"},{"issue":"4","key":"ppat.1009709.ref003","article-title":"Vaccination against helminth parasite infections","volume":"13","journal-title":"Expert Review of 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