{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T03:17:04Z","timestamp":1775445424973,"version":"3.50.1"},"reference-count":47,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T00:00:00Z","timestamp":1775174400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hospital da Luz Learning Health","award":["LH.INV.F2019036"],"award-info":[{"award-number":["LH.INV.F2019036"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pregnancy represents a dynamic immunological state in which the maternal immune system must balance tolerance toward the semi-allogeneic fetus while maintaining antimicrobial defense. Cytomegalovirus (CMV) infection is highly prevalent worldwide and profoundly shapes immune cell differentiation and long-term activation in adults. However, its interaction with pregnancy-associated immune remodeling remains incompletely defined. In this prospective longitudinal study, we comprehensively analyzed immune profiles of healthy pregnant women across all three trimesters and age-matched nonpregnant controls, stratified by CMV IgG serostatus. Multiparametric flow cytometry characterized T and B cell subsets and cytokine production following in vitro stimulation, while circulating cytokines and adhesion molecules were quantified using multiplex immunoassay. Gestational age was the primary determinant of leukocyte dynamics. Nevertheless, CMV-seropositive pregnant women showed enhanced activation and differentiation of CD4+ and, more prominently, CD8+ T cell subsets, changes not observed in nonpregnant women. Despite pronounced cellular differences, serum cytokine and adhesion molecule levels were largely comparable between CMV-seropositive and CMV-seronegative participants in both pregnant and nonpregnant groups. Functionally, CMV-seropositive women exhibited enrichment of IFN-\u03b3\u2013 and IL-21\u2013producing T cells, whereas B cell responses remained predominantly IL-10\u2013dominated. These findings indicate selective alterations in maternal lymphocyte activation and function during pregnancy in CMV-seropositive women, without evidence of systemic inflammation.<\/jats:p>","DOI":"10.3390\/ijms27073257","type":"journal-article","created":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T02:06:21Z","timestamp":1775441181000},"page":"3257","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Prior Cytomegalovirus Infection Shapes Lymphocyte Activation and Function During Pregnancy"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9933-4075","authenticated-orcid":false,"given":"Miguel","family":"\u00c2ngelo-Dias","sequence":"first","affiliation":[{"name":"Immunology Department, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, NMS, FCM, Universidade NOVA de Lisboa, 1169-056 Lisbon, Portugal"},{"name":"Comprehensive Health Research Centre\u2014CHRC, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, NMS, FCM, Universidade NOVA de Lisboa, 1169-056 Lisbon, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0353-0421","authenticated-orcid":false,"given":"Catarina Greg\u00f3rio","family":"Martins","sequence":"additional","affiliation":[{"name":"Immunology Department, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, NMS, FCM, Universidade NOVA de Lisboa, 1169-056 Lisbon, Portugal"},{"name":"Comprehensive Health Research Centre\u2014CHRC, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, NMS, FCM, Universidade NOVA de Lisboa, 1169-056 Lisbon, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5105-5137","authenticated-orcid":false,"given":"Mariana Apolin\u00e1rio","family":"Mata","sequence":"additional","affiliation":[{"name":"Immunology Department, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, NMS, FCM, Universidade NOVA de Lisboa, 1169-056 Lisbon, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madalena","family":"Barata","sequence":"additional","affiliation":[{"name":"Immunology Department, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, NMS, FCM, Universidade NOVA de Lisboa, 1169-056 Lisbon, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, High-Risk Pregnancy Centre, Hospital da Luz Lisboa, 1500-650 Lisbon, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susana","family":"Sarzedas","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, High-Risk Pregnancy Centre, Hospital da Luz Lisboa, 1500-650 Lisbon, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u00c9lia","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, High-Risk Pregnancy Centre, Hospital da Luz Lisboa, 1500-650 Lisbon, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Augusta","family":"Marques","sequence":"additional","affiliation":[{"name":"Infection Department, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, NMS, FCM, Universidade NOVA de Lisboa, 1169-056 Lisbon, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8015-7109","authenticated-orcid":false,"given":"Maria de Jesus","family":"Chasqueira","sequence":"additional","affiliation":[{"name":"Comprehensive Health Research Centre\u2014CHRC, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, NMS, FCM, Universidade NOVA de Lisboa, 1169-056 Lisbon, Portugal"},{"name":"Infection Department, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, NMS, FCM, Universidade NOVA de Lisboa, 1169-056 Lisbon, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4294-0872","authenticated-orcid":false,"given":"Paulo","family":"Paix\u00e3o","sequence":"additional","affiliation":[{"name":"Comprehensive Health Research Centre\u2014CHRC, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, NMS, FCM, Universidade NOVA de Lisboa, 1169-056 Lisbon, Portugal"},{"name":"Infection Department, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, NMS, FCM, Universidade NOVA de Lisboa, 1169-056 Lisbon, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0831-2741","authenticated-orcid":false,"given":"Jorge","family":"Lima","sequence":"additional","affiliation":[{"name":"Immunology Department, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, NMS, FCM, Universidade NOVA de Lisboa, 1169-056 Lisbon, Portugal"},{"name":"Comprehensive Health Research Centre\u2014CHRC, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, NMS, FCM, Universidade NOVA de Lisboa, 1169-056 Lisbon, Portugal"},{"name":"Department of Obstetrics and Gynecology, High-Risk Pregnancy Centre, Hospital da Luz Lisboa, 1500-650 Lisbon, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis Miguel","family":"Borrego","sequence":"additional","affiliation":[{"name":"Immunology Department, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, NMS, FCM, Universidade NOVA de Lisboa, 1169-056 Lisbon, Portugal"},{"name":"Comprehensive Health Research Centre\u2014CHRC, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, NMS, FCM, Universidade NOVA de Lisboa, 1169-056 Lisbon, Portugal"},{"name":"Department of Immunoallergy, Hospital da Luz Lisboa, 1500-650 Lisbon, 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