{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T05:34:08Z","timestamp":1789450448485,"version":"build-2803163510"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,11,3]],"date-time":"2021-11-03T00:00:00Z","timestamp":1635897600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100018536","name":"National Mega Project on Major Infectious Disease Prevention","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100018536","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>This study aimed to assess the host immune signatures associated with EBV infection and its clinical value in indicating the severity of children with acute infectious mononucleosis (IM).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Twenty-eight pediatric patients with IM aged 3\u20138 years were enrolled. The immune phenotypes and cytokine secretion capability of T cells were detected.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The percentages and absolute numbers of CD3<jats:sup>+<\/jats:sup>and CD8<jats:sup>+<\/jats:sup>T cells were significantly increased in IM patients compared with HCs. The percentages of Na\u00efve CD4<jats:sup>+<\/jats:sup>and CD8<jats:sup>+<\/jats:sup>T cells were decreased but with increased percentages of memory CD4<jats:sup>+<\/jats:sup>and CD8<jats:sup>+<\/jats:sup>T subsets. Our results showed the upregulation of active marker HLA-DR, TCR-\u03b1\u03b2, and inhibitory receptors PD-1, TIGIT in CD8<jats:sup>+<\/jats:sup>T cells from IM patients, which suggested that effective cytotoxic T cells were highly against EBV infection. However, EBV exposure impaired the cytokine (IFN-\u03b3, IL-2, and TNF-\u03b1) secretion capability of CD4<jats:sup>+<\/jats:sup>and CD8<jats:sup>+<\/jats:sup>T cells after stimulation with PMA\/ionomycin<jats:italic>in vitro<\/jats:italic>. Multivariate analysis revealed that the percentage of HLA-DR<jats:sup>+<\/jats:sup>CD8<jats:sup>+<\/jats:sup>T cells was an independent prognostic marker for IM. The percentage of HLA-DR<jats:sup>+<\/jats:sup>CD8<jats:sup>+<\/jats:sup>T cells was significantly correlated with high viral load and abnormal liver function results.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Robust expansion and upregulation of HLA-DR in CD8<jats:sup>+<\/jats:sup>T cells, accompanied with impaired cytokine secretion, were typical characteristics of children with acute IM. The percentage of HLA-DR<jats:sup>+<\/jats:sup>CD8<jats:sup>+<\/jats:sup>T cells might be used as a prominent marker not only for the early diagnosis but also for indicating the severity of IM.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2021.753290","type":"journal-article","created":{"date-parts":[[2021,11,3]],"date-time":"2021-11-03T09:18:55Z","timestamp":1635931135000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":24,"title":["HLA-DR Expression Level in CD8+ T Cells Correlates With the Severity of Children With Acute Infectious Mononucleosis"],"prefix":"10.3389","volume":"12","author":[{"given":"Yun","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoxing","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renren","family":"Ouyang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minxia","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhuan","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiwen","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Botao","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiji","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyan","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,11,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1993","DOI":"10.1056\/NEJMcp1001116","article-title":"Infectious Mononucleosis","volume":"362","author":"Luzuriaga","year":"2010","journal-title":"N Engl J Med"},{"key":"B2","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1097\/MOH.0b013e32834daa08","article-title":"Current Diagnosis and Management of Infectious Mononucleosis","volume":"19","author":"Vouloumanou","year":"2012","journal-title":"Curr Opin Hematol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.26558","article-title":"Diagnostic Value of Serological and Molecular Biological Tests for Infectious Mononucleosis by EBV in Different Age Stages and Course of the Disease","volume":"93","author":"Shi","year":"2021","journal-title":"J Med Virol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1177\/0300060520924550","article-title":"Clinical Manifestations and Laboratory Results of 61 Children With Infectious Mononucleosis","volume":"48","author":"Wu","year":"2020","journal-title":"J Int Med Res"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.issn.0578-1310.2016.08.001","article-title":"[Attach Importance to Diseases Associated With Severe Epstein-Barr Virus Infection in Children]","volume":"54","author":"Liu","year":"2016","journal-title":"Zhonghua Er Ke Za Zhi"},{"key":"B6","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.jcv.2018.03.001","article-title":"Primary Epstein-Barr Virus Infection","volume":"102","author":"Dunmire","year":"2018","journal-title":"J Clin Virol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1177\/1941738119873665","article-title":"Association of Splenic Rupture and Infectious Mononucleosis: A Retrospective Analysis and Review of Return-to-Play Recommendations","volume":"11","author":"Sylvester","year":"2019","journal-title":"Sports Health"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1086\/491740","article-title":"A Prospective Clinical Study of Epstein-Barr Virus and Host Interactions During Acute Infectious Mononucleosis","volume":"192","author":"Balfour","year":"2005","journal-title":"J Infect Dis"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197606172942501","article-title":"Infectious Mononucleosis. 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