{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T06:14:03Z","timestamp":1776147243987,"version":"3.50.1"},"reference-count":22,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Congenital cytomegalovirus (cCMV) is a major cause of intellectual disability. \u03b3\u03b4 T-cells contribute to early-life antiviral defense, yet their T-cell receptor (TCR) repertoire in preterm cCMV remains incompletely defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We profiled the \u03b3\u03b4 T-cell TCR repertoire in preterm infants allocated to three non-overlapping groups: Congenital CMV infection (cCMV) group (n=9), Acquired CMV infection (aCMV) group (n=10), and Preterm controls (CMV-negative) (n=7). RNA was extracted from RNAlater-stabilized heel-prick whole blood. Libraries were generated using constant-region\u2013anchored primers for TRD\/TRG, multiplex target enrichment, and index PCR, and sequenced on an Illumina platform (paired-end 150 bp). Repertoire features included CDR3 length distributions, V(D)J usage, VJ pairing, and clonal diversity. Nine lineage-associated rearrangements were quantified by intercalating dye\u2013based qPCR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>TRD: the 25-aa CDR3 bin was less frequent in the cCMV group versus controls, and the cCMV group showed a lower Gini index, indicating less clonal dominance (greater evenness) than controls. TRG: cCMV and aCMV differed in a length-interval\u2013dependent manner. V-gene usage shifted by group (TRAV29\/DV5 and TRAV38-2\/DV8 in TRD; TRGV2\/4\/8\/9 in TRG), and VJ pairings were more frequent in cCMV than in aCMV. The cCMV group harbored more \u201cspecific\u201d clonotypes than controls (P\u00a0=\u00a00.020). qPCR showed higher expression of D\u03b42\u2013D\u03b43, V\u03b42\u2013J\u03b41, V\u03b3\u2013J\u03b31.3\/2.3 in cCMV; the mixed V\u03b39+V\u03b311\u2013J\u03b31.1\/2.1 signal was also elevated but requires deconvolution.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>cCMV is associated with chain-specific remodeling of the \u03b3\u03b4 T-cell repertoire in preterm infants. These data may inform molecular risk stratification in neonatal CMV. Findings should be interpreted in light of small sample size and RNA-level profiling.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1713669","type":"journal-article","created":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T05:39:33Z","timestamp":1776145173000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Chain-specific remodeling of the \u03b3\u03b4 T-cell TCR repertoire in preterm infants with cCMV: a gestational-age\u2013stratified case\u2013control study"],"prefix":"10.3389","volume":"17","author":[{"given":"Peihui","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Shenzhen Maternity and Child Healthcare Hospital, Women and Children\u2019s Medical Center, Southern Medical University","place":["Shenzhen, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rong","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Shenzhen Maternity and Child Healthcare Hospital, Women and Children\u2019s Medical Center, Southern Medical University","place":["Shenzhen, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Zhao","sequence":"additional","affiliation":[{"name":"Neonatal Intensive Care Unit, Shenzhen Maternity and Child Healthcare Hospital, Women and Children\u2019s Medical Center, Southern Medical University","place":["Shenzhen, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Shenzhen Maternity and Child Healthcare Hospital, Women and Children\u2019s Medical Center, Southern Medical University","place":["Shenzhen, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Shenzhen Maternity and Child Healthcare Hospital, Women and Children\u2019s Medical Center, Southern Medical University","place":["Shenzhen, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Powei","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Shenzhen Maternity and Child Healthcare Hospital, Women and Children\u2019s Medical Center, Southern Medical University","place":["Shenzhen, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kai","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Shenzhen Maternity and Child Healthcare Hospital, Women and Children\u2019s Medical Center, Southern Medical University","place":["Shenzhen, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiujie","family":"Gao","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Guangdong Pharmaceutical University","place":["Guangzhou, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1097\/qco.0000000000000874","article-title":"Congenital cytomegalovirus infection diagnostics and management","volume":"35","author":"Pinninti","year":"2022","journal-title":"Curr Opin Infect Dis"},{"key":"B2","doi-asserted-by":"publisher","first-page":"2116","DOI":"10.3390\/v15102116","article-title":"Antiviral treatment of maternal and congenital cytomegalovirus (CMV) infections","volume":"15","author":"Pinninti","year":"2023","journal-title":"Viruses"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1159\/000477168","article-title":"Perinatal outcomes of non-primary maternal cytomegalovirus infection: a 15-year experience","volume":"43","author":"Simonazzi","year":"2018","journal-title":"Fetal Diagn Ther"},{"key":"B4","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1186\/s12887-021-02984-7","article-title":"Transmission of cytomegalovirus via breast milk in low birth weight and premature infants: a systematic review and meta-analysis","volume":"21","author":"Hu","year":"2021","journal-title":"BMC Pediatr"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2023.102303","article-title":"Antigen-specific gammadelta T cells contribute to cytomegalovirus control after stem cell transplantation","volume":"82","author":"Prinz","year":"2023","journal-title":"Curr Opin Immunol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2315592121","article-title":"Gammadelta T cell antigen receptor polyspecificity enables T cell responses to a broad range of immune challenges","volume":"121","author":"Guo","year":"2024","journal-title":"Proc Natl Acad Sci USA"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2024.02.003","article-title":"The immune system in neurological diseases: what innate-like T cells have to say","volume":"153","author":"Wyatt-Johnson","year":"2024","journal-title":"J Allergy Clin Immunol"},{"key":"B8","doi-asserted-by":"crossref","DOI":"10.1101\/2024.09.03.611042","article-title":"Efficient multiplex non-viral engineering and expansion of polyclonal \u03b3\u03b4 CAR-T cells for immunotherapy","volume-title":"Preprint. bioRxiv","author":"Bridge","year":"2024"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-024-01855-4","article-title":"Perinatal thymic-derived CD8alphabeta-expressing gammadelta T cells are innate IFN-gamma producers that expand in IL-7R-STAT5B-driven neoplasms","volume":"25","author":"Sumaria","year":"2024","journal-title":"Nat Immunol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07439-4","article-title":"Structures of human gammadelta T cell receptor-CD3 complex","volume":"630","author":"Xin","year":"2024","journal-title":"Nature"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1105105108","article-title":"Evolution of the V, D, and J gene segments used in the primate gammadelta T-cell receptor reveals a dichotomy of conservation and diversity","volume":"108","author":"Kazen","year":"2011","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.adn3954","article-title":"Human gammadelta T cells in diverse tissues exhibit site-specific maturation dynamics across the life span","volume":"9","author":"Gray","year":"2024","journal-title":"Sci Immunol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20231987","article-title":"Gammadelta T cell profiling in a cohort of preterm infants reveals elevated frequencies of CD83+ gammadelta T cells in sepsis","volume":"221","author":"Leon-Lara","year":"2024","journal-title":"J Exp Med"},{"key":"B14","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1186\/s12887-024-05051-z","article-title":"Changes of CD8(+)CD28(-) Tregs and gamma-delta-T-cells in a neonate with intrauterine cytomegalovirus infection: a case report","volume":"24","author":"Chen","year":"2024","journal-title":"BMC Pediatr"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/s1473-3099(17)30143-3","article-title":"Congenital cytomegalovirus infection in pregnancy and the neonate: consensus recommendations for prevention, diagnosis, and therapy","volume":"17","author":"Rawlinson","year":"2017","journal-title":"Lancet Infect Dis"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20212525","article-title":"A CMV-induced adaptive human Vdelta1+ gammadelta T cell clone recognizes HLA-DR","volume":"219","author":"Deseke","year":"2022","journal-title":"J Exp Med"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1007\/s00251-019-01134-9","article-title":"Revealing factors determining immunodominant responses against dominant epitopes","volume":"72","author":"Ritmahan","year":"2020","journal-title":"Immunogenetics"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2401750","article-title":"Rapid, multifluorescent TCRG Vgamma and Jgamma typing: application to T cell acute lymphoblastic leukemia and to the detection of minor clonal populations","volume":"14","author":"Delabesse","year":"2000","journal-title":"Leukemia"},{"key":"B19","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/s2352-4642(24)00237-2","article-title":"Universal newborn screening for congenital cytomegalovirus infection","volume":"9","author":"Schleiss","year":"2025","journal-title":"Lancet Child Adolesc Health"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1136\/archdischild-2022-323809","article-title":"Managing challenges in congenital CMV: current thinking","volume":"108","author":"Jones","year":"2023","journal-title":"Arch Dis Child"},{"key":"B21","article-title":"Primary cytomegalovirus infection in the postnatal period","volume":"150","author":"Bergman","year":"2006","journal-title":"Ned Tijdschr Geneeskd"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/srep29544","article-title":"Analyzing the CDR3 repertoire with respect to TCR-Beta chain V-D-J and V-J rearrangements in peripheral T cells using HTS","volume":"6","author":"Ma","year":"2016","journal-title":"Sci Rep"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1713669\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T05:39:34Z","timestamp":1776145174000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1713669\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,14]]},"references-count":22,"alternative-id":["10.3389\/fimmu.2026.1713669"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1713669","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,14]]},"article-number":"1713669"}}