{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T22:44:24Z","timestamp":1792449864674,"version":"4.5.0"},"reference-count":135,"publisher":"American Chemical Society (ACS)","issue":"4","license":[{"start":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:00:00Z","timestamp":1778025600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000052","name":"NIH Office of the Director","doi-asserted-by":"publisher","award":["UG3OD02349"],"award-info":[{"award-number":["UG3OD02349"]}],"id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000052","name":"NIH Office of the Director","doi-asserted-by":"publisher","award":["UH3OD023349"],"award-info":[{"award-number":["UH3OD023349"]}],"id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["T32AI007285"],"award-info":[{"award-number":["T32AI007285"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["P30ES001247"],"award-info":[{"award-number":["P30ES001247"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["R01ES036197"],"award-info":[{"award-number":["R01ES036197"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000071","name":"National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R01HD083369"],"award-info":[{"award-number":["R01HD083369"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1TR002001"],"award-info":[{"award-number":["UL1TR002001"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009750","name":"University of Rochester Medical Center","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100009750","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>BACKGROUND: Environmental exposures to toxicants, such as per- and polyfluoroalkyl substances (PFAS), during gestation can disrupt immune development, causing long-term impacts on a child\u2019s ability to generate a well-regulated, protective immune response. T-cells coordinate with all immune cell types to orchestrate both cellular and antibody-mediated responses. While there is compelling evidence that PFAS alters immunity in humans, the specific effects of early life PFAS exposure on infant T-cell development are unreported. Because of their central role in immunity, altered T-cell development in infants would have implications on immune responses broadly and long-term. OBJECTIVES: We seek to model longitudinal changes in the frequency of functionally distinct CD4+ T-cell subpopulations from birth through 12 months and their association with in utero PFAS exposure. METHODS: Maternal-infant dyads were recruited as part of the UPSIDE-ECHO cohort during the first trimester between 2015 and 2019 in Rochester, New York; dyads were followed through the infant\u2019s first birthday. Maternal PFAS concentrations (PFOS, PFOA, PFNA, PFHXS and PFDA) were quantified in serum during the second trimester using high-performance liquid chromatography and tandem mass spectrometry. Infant lymphocyte frequencies were assessed at birth, 6- and 12-months using mass cytometry and high-dimensional clustering methods. Linear mixed-effects models were employed to analyze the relationship between maternal PFAS concentrations and CD4+ T-cell subpopulations (n = 200). All models included a PFAS and age interaction and were adjusted for parity, infant sex, and prepregnancy body mass index. RESULTS: In utero PFAS exposure correlated with multiple CD4+ T-cell subpopulations in infants. The greatest effect sizes were seen in T follicular helper (Tfh) and T-helper 2 (Th2) cells at 12 months. A log2-unit increase in PFOS was associated with lower Tfh [0.17% (95% CI: \u22120.30, \u22120.40)] and greater Th2 [0.27% (95% CI: 0.18, 0.35)] cell percentages at 12 months. Similar trends were observed for PFOA, PFNA, PFHXS, and PFDA. DISCUSSION: Maternal PFAS exposures correlate with cell-specific changes in the infant T-cell compartment, including key CD4+ T-cell subpopulations that play central roles in coordinating well-regulated protective immunity. Future studies into the role of PFAS-associated T-cell distribution and the risk of adverse immune-related health outcomes in children are warranted.<\/jats:p>","DOI":"10.1021\/ehp.6c00037","type":"journal-article","created":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T19:51:07Z","timestamp":1778097067000},"page":"408-422","source":"Crossref","is-referenced-by-count":8,"title":["In Utero Per- and Polyfluoroalkyl\nSubstances (PFAS)\nExposure and Changes in Infant T Helper Cell Development among UPSIDE-ECHO\nCohort Participants"],"prefix":"10.1021","volume":"134","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9743-833X","authenticated-orcid":true,"given":"Darline","family":"Castro-Melendez","sequence":"first","affiliation":[{"name":"University of Rochester School of Medicine and Dentistry , , , ,","place":["Rochester, New York, United States, 14642"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Laniewski","sequence":"additional","affiliation":[{"name":"University of Rochester School of Medicine and Dentistry , , , ,","place":["Rochester, New York, United States, 14642"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd","family":"Jusko","sequence":"additional","affiliation":[{"name":"University of Rochester School of Medicine and Dentistry , , , ,","place":["Rochester, New York, United States, 14642"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing","family":"Qiu","sequence":"additional","affiliation":[{"name":"University of Rochester School of Medicine and Dentistry , , , ,","place":["Rochester, New York, United States, 14642"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. Paige","family":"Lawrence","sequence":"additional","affiliation":[{"name":"University of Rochester School of Medicine and Dentistry , , , ,","place":["Rochester, New York, United States, 14642"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0718-1807","authenticated-orcid":true,"given":"Zorimar","family":"Rivera-Nu\u0301n\u0303ez","sequence":"additional","affiliation":[{"name":"Rutgers School of Public Health, Environmental and Occupational Health Sciences Institute , , , ,","place":["Piscataway, New Jersey, United States, 08854"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brunner","family":"Jessica","sequence":"additional","affiliation":[{"name":"University of Rochester School of Medicine and Dentistry , , , ,","place":["Rochester, New York, United States, 14642"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghan","family":"Best","sequence":"additional","affiliation":[{"name":"University of Rochester School of Medicine and Dentistry , , , ,","place":["Rochester, New York, United States, 14642"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison","family":"Macomber","sequence":"additional","affiliation":[{"name":"University of Rochester School of Medicine and Dentistry , , , ,","place":["Rochester, New York, United States, 14642"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alena","family":"Leger","sequence":"additional","affiliation":[{"name":"University of Rochester School of Medicine and Dentistry , , , ,","place":["Rochester, New York, United States, 14642"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1926-7456","authenticated-orcid":true,"given":"Kurunthachalam","family":"Kannan","sequence":"additional","affiliation":[{"name":"University at Albany , , , ,","place":["Albany, New York, United States, 12222"]},{"name":"Wadsworth Center , , , ,","place":["Albany, New York, United States, 12208"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard K","family":"Miller","sequence":"additional","affiliation":[{"name":"University of Rochester School of Medicine and Dentistry , , , ,","place":["Rochester, New York, United States, 14642"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily S.","family":"Barret","sequence":"additional","affiliation":[{"name":"Rutgers School of Public Health, Environmental and Occupational Health Sciences Institute , , , ,","place":["Piscataway, New Jersey, United States, 08854"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas G.","family":"O\u2019Connor","sequence":"additional","affiliation":[{"name":"University of Rochester School of Medicine and Dentistry , , , ,","place":["Rochester, New York, United States, 14642"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin","family":"Scheible","sequence":"additional","affiliation":[{"name":"University of Rochester School of Medicine and Dentistry , , , ,","place":["Rochester, New York, United States, 14642"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,5,6]]},"reference":[{"issue":"6480","key":"2026080409223672300_cit1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aay3224","article-title":"A cell\natlas of human thymic development defines T cell repertoire formation","volume":"367","author":"Park","year":"2020","journal-title":"Science."},{"issue":"8","key":"2026080409223672300_cit2","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1038\/nri.2017.54","article-title":"Unique aspects\nof the perinatal immune\nsystem","volume":"17","author":"Zhang","year":"2017","journal-title":"Nat. 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Pollut."},{"key":"2026080409223672300_cit11","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2020.152565","article-title":"Early life exposure\nto per- and polyfluoroalkyl substances\n(PFAS) and latent health outcomes: A review including the placenta\nas a target tissue and possible driver of peri- and postnatal effects","volume":"443","author":"Blake","year":"2020","journal-title":"Toxicology."},{"key":"2026080409223672300_cit12","doi-asserted-by":"publisher","DOI":"10.1016\/j.envres.2022.115188","article-title":"A systematic\nevidence\nmap of chronic inflammation and immunosuppression related to per-\nand polyfluoroalkyl substance (PFAS) exposure","volume":"220","author":"Zhang","year":"2023","journal-title":"Environ. 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Health Perspect."},{"key":"2026080409223672300_cit15","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1016\/j.envint.2013.06.004","article-title":"Accumulation of perfluoroalkyl\nsubstances in human tissues","volume":"59","author":"Pe\u0301rez","year":"2013","journal-title":"Environment International."},{"issue":"6","key":"2026080409223672300_cit16","doi-asserted-by":"publisher","first-page":"6098","DOI":"10.3390\/ijerph120606098","article-title":"Serum Biomarkers\nof Exposure to Perfluoroalkyl\nSubstances in Relation to Serum Testosterone and Measures of Thyroid\nFunction among Adults and Adolescents from NHANES 2011\u20132012","volume":"12","author":"Lewis","year":"2015","journal-title":"International Journal of Environmental Research and Public\nHealth."},{"issue":"1","key":"2026080409223672300_cit17","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1038\/s41370-023-00581-7","article-title":"Concentrations of per-\nand polyfluoroalkyl substances (PFAS) in paired tap water and blood\nsamples during pregnancy","volume":"34","author":"Cserbik","year":"2024","journal-title":"J. Expo Sci. Environ.\nEpidemiol."},{"key":"2026080409223672300_cit18","doi-asserted-by":"publisher","DOI":"10.1016\/j.envint.2020.106123","article-title":"Human biomonitoring of per- and polyfluoroalkyl\nsubstances\nin German blood plasma samples from 1982 to 2019","volume":"145","author":"Go\u0308ckener","year":"2020","journal-title":"Environment International."},{"key":"2026080409223672300_cit19","doi-asserted-by":"publisher","DOI":"10.1016\/j.envint.2019.105295","article-title":"Distribution of novel\nand legacy per-\/polyfluoroalkyl substances in serum and its associations\nwith two glycemic biomarkers among Chinese adult men and women with\nnormal blood glucose levels","volume":"134","author":"Duan","year":"2020","journal-title":"Environment International."},{"issue":"10","key":"2026080409223672300_cit20","doi-asserted-by":"publisher","first-page":"6014","DOI":"10.1021\/acs.est.1c01057","article-title":"A Critical Review on Transplacental Transfer\nof Per- and Polyfluoroalkyl Substances: Prenatal Exposure Levels,\nCharacteristics, and Mechanisms","volume":"56","author":"Ma","year":"2022","journal-title":"Environ. 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Sci. Technol."},{"issue":"1","key":"2026080409223672300_cit24","doi-asserted-by":"publisher","first-page":"634","DOI":"10.1021\/acs.est.6b04590","article-title":"Novel Chlorinated Polyfluorinated Ether Sulfonates\nand Legacy Per-\/Polyfluoroalkyl Substances: Placental Transfer and\nRelationship with Serum Albumin and Glomerular Filtration Rate","volume":"51","author":"Pan","year":"2017","journal-title":"Environ. Sci. 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Immunotoxicol."},{"issue":"2","key":"2026080409223672300_cit30","doi-asserted-by":"publisher","first-page":"270","DOI":"10.3109\/1547691X.2015.1067259","article-title":"Antibody response to\nbooster vaccination with tetanus and diphtheria in adults exposed\nto perfluorinated alkylates","volume":"13","author":"Kielsen","year":"2016","journal-title":"Journal of Immunotoxicology."},{"key":"2026080409223672300_cit31","doi-asserted-by":"publisher","DOI":"10.1016\/j.envres.2022.115067","article-title":"Cross-sectional associations\nof maternal PFAS exposure on SARS-CoV-2 IgG antibody levels during\npregnancy","volume":"219","author":"Kaur","year":"2023","journal-title":"Environ. 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Epidemiol."},{"issue":"Pt 1","key":"2026080409223672300_cit34","doi-asserted-by":"publisher","DOI":"10.1016\/j.envres.2023.117297","article-title":"Serum per- and polyfluoroalkyl\nsubstance concentrations and longitudinal change in post-infection\nand post-vaccination SARS-CoV-2 antibodies","volume":"239","author":"Hollister","year":"2023","journal-title":"Environ. Res."},{"issue":"1","key":"2026080409223672300_cit35","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1080\/1547691X.2021.1922957","article-title":"Serum vaccine antibody\nconcentrations in adults exposed to per- and polyfluoroalkyl substances:\nA birth cohort in the Faroe Islands","volume":"18","author":"Shih","year":"2021","journal-title":"J. Immunotoxicol."},{"key":"2026080409223672300_cit36","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/j.envres.2016.05.020","article-title":"Perfluoroalkyl substance serum concentrations\nand immune response to FluMist vaccination among healthy adults","volume":"149","author":"Stein","year":"2016","journal-title":"Environ. Res."},{"issue":"Pt 1","key":"2026080409223672300_cit37","doi-asserted-by":"publisher","DOI":"10.1016\/j.envres.2024.120039","article-title":"Antibody\nresponse to\nSARS-CoV-2 mRNA vaccination in Danish adults exposed to perfluoroalkyl\nsubstances (PFASs): The ENFORCE study","volume":"263","author":"Timmermann","year":"2024","journal-title":"Environ.\nRes."},{"issue":"3","key":"2026080409223672300_cit38","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1038\/nri3795","article-title":"The generation of\nantibody-secreting plasma cells","volume":"15","author":"Nutt","year":"2015","journal-title":"Nat. Rev. Immunol."},{"issue":"1","key":"2026080409223672300_cit39","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1038\/nri3567","article-title":"Human memory T cells: generation,\ncompartmentalization and homeostasis","volume":"14","author":"Farber","year":"2014","journal-title":"Nat. Rev.\nImmunol."},{"issue":"1","key":"2026080409223672300_cit40","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1111\/j.1600-065X.2010.00951.x","article-title":"Peripheral CD4+ T-cell differentiation regulated by\nnetworks of cytokines and transcription factors: Transcription factor\nnetwork in Th cells","volume":"238","author":"Zhu","year":"2010","journal-title":"Immunological Reviews."},{"key":"2026080409223672300_cit41","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1146\/annurev.iy.11.040193.001555","article-title":"T cell-dependent\nB cell activation","volume":"11","author":"Parker","year":"1993","journal-title":"Annu. Rev. 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