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We investigated the phenotypic heterogeneity of exhausted CD8<jats:sup>+<\/jats:sup> T cells in HBV carriers.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We enrolled 31 HBV carriers and 23 healthy controls (HCs) in our study. Peripheral blood mononuclear cells (PBMCs) were isolated, and flow cytometry was used to determine the phenotypic distribution of CD8<jats:sup>+<\/jats:sup> T cell subsets. Expression of cytokines such as TNF-\u03b1 and IFN-\u03b3 was detected by quantitative reverse transcription\u2013PCR, a fluorescence flow cytometry-based immunomicrobead assay and flow cytometry.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>There were no significant differences in the baseline characteristics between the 31 HBV carriers and the 23 sex- and age-matched HCs. CD8<jats:sup>+<\/jats:sup> T cells exhibited higher levels of inhibitory receptors (TIM3 and PD1) in the HBV carriers than in the HCs (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05); in particular, Tfc cells (CXCR5<jats:sup>+<\/jats:sup>CD25<jats:sup>\u2212<\/jats:sup>) expressed higher levels of TIM3 and PD1 than non-Tfc cells in the HBV carriers. In addition, among the subsets of Tc cells, the Tc17 (CXCR5<jats:sup>\u2212<\/jats:sup>CD25<jats:sup>\u2212<\/jats:sup>CCR6<jats:sup>+<\/jats:sup>) subset displayed increased expression of TIM3 and LAG3 in the HBV carriers. Our findings further showed that CD8<jats:sup>+<\/jats:sup> T cells produced lower levels of IFN-\u03b3, TNF-\u03b1, and Granzyme B. Paired analysis of the Tfc subset and the Tc subset indicated that higher levels of cytokines (IFN-\u03b3 and TNF-\u03b1) were produced by the Tfc subset in the HBV carriers. Among the Tc subsets, the Tc17 subset produced lower levels of cytokines.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>The Tfc subset exhibited an enhanced exhausted phenotype but possessed some functional properties during chronic HBV infection, while the Tc subset showed a lower functional level. The identification of these unique subsets may provide a potential immunotherapeutic target in chronic HBV infection.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12865-022-00488-2","type":"journal-article","created":{"date-parts":[[2022,4,20]],"date-time":"2022-04-20T15:03:33Z","timestamp":1650467013000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Exhausted phenotype of circulating CD8+ T cell subsets in hepatitis B virus carriers"],"prefix":"10.1186","volume":"23","author":[{"given":"Daixi","family":"Jiang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Can","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danying","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxiao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawei","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigui","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,4,20]]},"reference":[{"key":"488_CR1","doi-asserted-by":"publisher","first-page":"18035","DOI":"10.1038\/nrdp.2018.35","volume":"4","author":"MF Yuen","year":"2018","unstructured":"Yuen MF, Chen DS, Dusheiko GM, Janssen HLA, Lau DTY, Locarnini SA, Peters MG, Lai CL. 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Immunity. 2021;54(8):1698\u2013714.","journal-title":"Immunity"}],"container-title":["BMC Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12865-022-00488-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12865-022-00488-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12865-022-00488-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,21]],"date-time":"2022-04-21T13:10:22Z","timestamp":1650546622000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcimmunol.biomedcentral.com\/articles\/10.1186\/s12865-022-00488-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,20]]},"references-count":41,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["488"],"URL":"https:\/\/doi.org\/10.1186\/s12865-022-00488-2","relation":{},"ISSN":["1471-2172"],"issn-type":[{"value":"1471-2172","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,20]]},"assertion":[{"value":"9 August 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 March 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 April 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was conducted in compliance with the Declaration of Helsinki and was approved by the Ethical Committee of the First Affiliated Hospital of Zhejiang University of Medicine (Approval No: [2021]523). All involved participants provided written informed consent.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"18"}}