{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T11:23:45Z","timestamp":1790421825971,"version":"4.1.0"},"reference-count":69,"publisher":"American Society for Clinical Investigation","issue":"16","license":[{"start":{"date-parts":[[2021,8,23]],"date-time":"2021-08-23T00:00:00Z","timestamp":1629676800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,8,23]]},"abstract":"<jats:p>\n                    A major\n                    <jats:bold>\u03b3\u03b4<\/jats:bold>\n                    T cell population in human adult blood are the V\n                    <jats:bold>\u03b3<\/jats:bold>\n                    9V\n                    <jats:bold>\u03b4<\/jats:bold>\n                    2 T cells that are activated and expanded in a TCR-dependent manner by microbe-derived and endogenously derived phosphorylated prenyl metabolites (phosphoantigens). V\n                    <jats:bold>\u03b3<\/jats:bold>\n                    9V\n                    <jats:bold>\u03b4<\/jats:bold>\n                    2 T cells are also abundant in human fetal peripheral blood, but compared with their adult counterparts they have a distinct developmental origin, are hyporesponsive toward in vitro phosphoantigen exposure, and do not possess a cytotoxic effector phenotype. In order to obtain insight into the role of V\n                    <jats:bold>\u03b3<\/jats:bold>\n                    9V\n                    <jats:bold>\u03b4<\/jats:bold>\n                    2 T cells in the human fetus, we investigated their response to in utero infection with the phosphoantigen-producing parasite\n                    <jats:italic>Toxoplasma gondii<\/jats:italic>\n                    (\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>gondii<\/jats:italic>\n                    ). V\n                    <jats:bold>\u03b3<\/jats:bold>\n                    9V\n                    <jats:bold>\u03b4<\/jats:bold>\n                    2 T cells expanded strongly when faced with congenital\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>gondii<\/jats:italic>\n                    infection, which was associated with differentiation toward potent cytotoxic effector cells. The V\n                    <jats:bold>\u03b3<\/jats:bold>\n                    9V\n                    <jats:bold>\u03b4<\/jats:bold>\n                    2 T cell expansion in utero resulted in a fetal footprint with public germline-encoded clonotypes in the V\n                    <jats:bold>\u03b3<\/jats:bold>\n                    9V\n                    <jats:bold>\u03b4<\/jats:bold>\n                    2 TCR repertoire 2 months after birth. Overall, our data indicate that the human fetus, from early gestation onward, possesses public V\n                    <jats:bold>\u03b3<\/jats:bold>\n                    9V\n                    <jats:bold>\u03b4<\/jats:bold>\n                    2 T cells that acquire effector functions following parasite infections.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.138066","type":"journal-article","created":{"date-parts":[[2021,7,13]],"date-time":"2021-07-13T12:01:10Z","timestamp":1626177670000},"source":"Crossref","is-referenced-by-count":20,"title":["Effector V\u03b39V\u03b42 T cell response to congenital Toxoplasma gondii infection"],"prefix":"10.1172","volume":"6","author":[{"given":"Ling","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Pharmacotherapy and Pharmaceutics,"},{"name":"Institute for Medical Immunology, and"},{"name":"ULB Center for Research in Immunology, Universit\u00e9 Libre de Bruxelles (ULB), Brussels, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3006-1993","authenticated-orcid":true,"given":"Maria","family":"Papadopoulou","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Pharmaceutics,"},{"name":"Institute for Medical Immunology, and"},{"name":"ULB Center for Research in Immunology, Universit\u00e9 Libre de Bruxelles (ULB), Brussels, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Taton","sequence":"additional","affiliation":[{"name":"Institute for Medical Immunology, and"},{"name":"ULB Center for Research in Immunology, Universit\u00e9 Libre de Bruxelles (ULB), Brussels, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Genco","sequence":"additional","affiliation":[{"name":"IRCCS San Matteo Polyclinic, Pavia, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaud","family":"Marchant","sequence":"additional","affiliation":[{"name":"Institute for Medical Immunology, and"},{"name":"ULB Center for Research in Immunology, Universit\u00e9 Libre de Bruxelles (ULB), Brussels, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Meroni","sequence":"additional","affiliation":[{"name":"IRCCS San Matteo Polyclinic, Pavia, Italy."},{"name":"Molecular Medicine Department, University of Pavia, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7605-8845","authenticated-orcid":true,"given":"David","family":"Vermijlen","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Pharmaceutics,"},{"name":"Institute for Medical Immunology, and"},{"name":"ULB Center for Research in Immunology, Universit\u00e9 Libre de Bruxelles (ULB), Brussels, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2021,8,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.18.1.975"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3904"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2017.10.009"},{"issue":"1\u20133","key":"B4","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/S0014-5793(03)00483-6","article-title":"Microbial isoprenoid biosynthesis and human gammadelta T cell activation","volume":"544","author":"Eberl","year":"2003","journal-title":"FEBS Lett"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2006.00479.x"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1000231"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200113584"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20110226"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3390\/ph8010040"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1412058112"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2007.02784.x"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1600284"},{"key":"B13"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.54"},{"key":"B15"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00588"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1900592"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-00452-4"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12926"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1126\/science.aay3224"},{"issue":"7","key":"B21","doi-asserted-by":"crossref","first-page":"2873","DOI":"10.4049\/jimmunol.157.7.2873","article-title":"Extrathymic origin of human gamma delta T cells during fetal development","volume":"157","author":"McVay","year":"1996","journal-title":"J Immunol"},{"issue":"12","key":"B22","doi-asserted-by":"crossref","first-page":"5851","DOI":"10.4049\/jimmunol.160.12.5851","article-title":"The generation of human gammadelta T cell repertoires during fetal development","volume":"160","author":"McVay","year":"1998","journal-title":"J Immunol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)16412-X"},{"key":"B24"},{"issue":"12","key":"B25","doi-asserted-by":"crossref","first-page":"5521","DOI":"10.4049\/jimmunol.157.12.5521","article-title":"Induction of gammadelta T cells during acute murine infection with Toxoplasma gondii","volume":"157","author":"Kasper","year":"1996","journal-title":"J Immunol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118076"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jit802"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.11.4.569"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00024-09"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20090348"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-01-136713"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1611098113"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14760"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1922595117"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1922588117"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(11)70341-3"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-0199"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.26.021607.090404"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2019.04.013"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200424861"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-08-376111"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2006.00470.x"},{"issue":"3","key":"B43","doi-asserted-by":"crossref","DOI":"10.1084\/jem.20190580","article-title":"The human fetal thymus generates invariant effector \u03b3\u03b4 T cells.","volume":"217","author":"Tieppo","year":"2020","journal-title":"J Exp Med"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13850"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.10.5136"},{"key":"B46"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1084\/jem.171.5.1597"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1800934"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004702"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004481"},{"key":"B51","doi-asserted-by":"crossref","DOI":"10.1155\/2014\/910621","article-title":"Biomarker analysis revealed distinct profiles of innate and adaptive immunity in infants with ocular lesions of congenital toxoplasmosis","volume":"2014","author":"Machado","year":"2014","journal-title":"Mediators Inflamm"},{"key":"B52","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2014.00552","article-title":"Immunity to cytomegalovirus in early life","volume":"5","author":"Huygens","year":"2014","journal-title":"Front Immunol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4110"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1700314"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.8b00655"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-05-430470"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2013.07.003"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12806"},{"key":"B59","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2014.00687","article-title":"\u03b3\u03b4 T cells in HIV disease: past, present, and future","volume":"5","author":"Pauza","year":"2015","journal-title":"Front Immunol"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1172\/JCI5409"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-01-255166"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2012.374"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2008101072"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2019000682"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1097\/INF.0b013e3181586052"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens8010024"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3364"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1004503"},{"key":"B69","first-page":"2579","article-title":"Visualizing data using t-SNE","volume":"9","author":"Van der Maaten","year":"2008","journal-title":"J Mach Learn Res"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/138066\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T23:45:30Z","timestamp":1779147930000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/138066"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,23]]},"references-count":69,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2021,8,23]]},"published-print":{"date-parts":[[2021,8,23]]}},"alternative-id":["10.1172\/jci.insight.138066"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.138066","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,23]]},"article-number":"e138066"}}