{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T14:13:58Z","timestamp":1766067238987,"version":"3.40.5"},"reference-count":33,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,11,25]],"date-time":"2020-11-25T00:00:00Z","timestamp":1606262400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003762","name":"Institut Pasteur","doi-asserted-by":"publisher","award":["20\u201016"],"award-info":[{"award-number":["20\u201016"]}],"id":[{"id":"10.13039\/501100003762","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background &amp; Aims<\/jats:title><jats:p>During chronic viral infections, the apoptosis of activated T cell elicits a CD8<jats:sup>+<\/jats:sup> T cell response directed to those cryptic epitopes that emerge from caspase\u2010cleaved structural proteins. Such response directed to apoptosis\u2010associated epitopes (AEs) contributes to the amplification of immunopathology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Here, we have analysed through flow cytometry AE\u2010specific CD8<jats:sup>+<\/jats:sup> T cells in patients with chronic hepatitis B virus (HBV) infection, na\u00efve\u2010to\u2010treatment or undergoing nucleos(t)ide\u2010analogue (NUC) therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that AE\u2010specific CD8<jats:sup>+<\/jats:sup> T cell frequencies were significantly increased only in those NUC\u2010treated patients who also presented advanced hepatic fibrosis. Regulatory T cells were also expanded in those patients, and AE\u2010specific, but not HBV\u2010specific, CD8<jats:sup>+<\/jats:sup> T cell frequency positively correlated with Treg percentages. Through multiparameter flow cytometry, multidimensionality reduction and unsupervised clustering analysis, we could identify novel subpopulations among effector memory (em) and emCD45RA<jats:sup>+<\/jats:sup> T cell (Tem and Temra) subsets. CD8<jats:sup>+<\/jats:sup> T cells with distinct specificities differentially populated the subpopulation map: while HBV\u2010specific were mostly contained in the Tem subset, AE\u2010specific CD8<jats:sup>+<\/jats:sup> T cells encompassed na\u00efve, as well as T central memory, Tem and Temra cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>All together, these findings indicate a link between AE\u2010specific CD8<jats:sup>+<\/jats:sup> T cells and advanced liver fibrosis in patients with chronic HBV infection, and suggest that virus\u2010specific and AE\u2010specific CD8<jats:sup>+<\/jats:sup> T cells exhibit distinct differentiation states and contribute in distinct ways to immunopathology.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.14720","type":"journal-article","created":{"date-parts":[[2020,11,7]],"date-time":"2020-11-07T08:10:56Z","timestamp":1604736656000},"page":"470-481","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["CD8<sup>+<\/sup> T cells specific to apoptosis\u2010associated epitopes are expanded in patients with chronic HBV infection and fibrosis"],"prefix":"10.1111","volume":"41","author":[{"given":"Ilenia","family":"Pacella","sequence":"first","affiliation":[{"name":"Department of Internal Clinical Sciences, Anaesthesiology and Cardiovascular Sciences Sapienza Universit\u00e0 di Roma Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilenia","family":"Cammarata","sequence":"additional","affiliation":[{"name":"Department of Internal Clinical Sciences, Anaesthesiology and Cardiovascular Sciences Sapienza Universit\u00e0 di Roma Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmela","family":"Martire","sequence":"additional","affiliation":[{"name":"Department of Internal Clinical Sciences, Anaesthesiology and Cardiovascular Sciences Sapienza Universit\u00e0 di Roma Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppina","family":"Brancaccio","sequence":"additional","affiliation":[{"name":"Unit of Infectious Diseases University Hospital Padua Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni Battista","family":"Gaeta","sequence":"additional","affiliation":[{"name":"Infectious Disease Unit Department of Mental and Physical Health and Preventive Medicine University of Campania Luigi Vanvitelli Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincenzo","family":"Barnaba","sequence":"additional","affiliation":[{"name":"Department of Internal Clinical Sciences, Anaesthesiology and Cardiovascular Sciences Sapienza Universit\u00e0 di Roma Rome Italy"},{"name":"Laboratory Affiliated to Istituto Pasteur Italia \u2013 Fondazione Cenci Bolognetti Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9685-5227","authenticated-orcid":false,"given":"Silvia","family":"Piconese","sequence":"additional","affiliation":[{"name":"Department of Internal Clinical Sciences, Anaesthesiology and Cardiovascular Sciences Sapienza Universit\u00e0 di Roma Rome Italy"},{"name":"Laboratory Affiliated to Istituto Pasteur Italia \u2013 Fondazione Cenci Bolognetti Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,11,25]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"World Health Organization.Hepatitis B.2019.https:\/\/www.who.int\/news\u2010room\/fact\u2010sheets\/detail\/hepatitis\u2010b. 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