{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T09:55:24Z","timestamp":1753869324709,"version":"3.41.2"},"reference-count":28,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,1,12]],"date-time":"2025-01-12T00:00:00Z","timestamp":1736640000000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunity Inflam &amp;amp; Disease"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Backgrounds and Aims<\/jats:title><jats:p>CD8+T cells are crucially associated with the fight against hepatitis B virus (HBV) infection. CD161 has been shown to express remarkably on HCV\u2010specific CD8+T cells. However, the accurate function of CD161+CD8+T cells in HBV immunity or pathogenesis remains undetermined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Blood samples were collected from 25 chronic hepatitis B (CHB) patients. Peripheral blood levels of CD161+CD8+T cells and their correlation with serum ALT levels were analyzed in CHB patients. To analyze the in vivo CD161+CD8+T cell's number, function, and intrahepatic recruitment characteristics, HBV replication mouse models were established. The expression of CD161 on HBV\u2010specific CD8+T cells was also detected by analyzing CD161+CD8+T cell functions during infection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Patients with CHB infection had a markedly lower peripheral blood frequency of CD161+CD8+T cells than did healthy controls and negatively correlated with serum ALT level. Furthermore, compared to the control mice, the frequency of CD161+CD8+T cells was significantly decreased in the blood of acute and chronic HBV\u2010replicating mice. Moreover, CHB\u2010replicating mice had significantly increased hepatic levels of CD161+CD8+T cells, which was not observed in the acute group of mice. Additionally, the CD161+CD8+T cells were categorized into CD161<jats:sup>hi<\/jats:sup> and CD161<jats:sup>int<\/jats:sup>CD8+T cells and it was revealed that in the liver of CHB\u2010replicating mice the primary recruited cells were CD161<jats:sup>hi<\/jats:sup>CD8+T. Intrahepatic CD161<jats:sup>hi<\/jats:sup>CD8+T cells demonstrated increased CXCR6 expression, enhanced production of cytokine IL\u201017 and TNF\u2010\u0251, and reduced IFN\u2010\u03b3 secretion. Accordingly, the CXCL16 mRNA expression in the liver tissue of CHB\u2010replication mice was markedly higher than in acute HBV\u2010replicating and control mice. The study also revealed that HBV\u2010specific CD8+T cells were mainly CD161\u2010CD8+T cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>During HBV infection, the intrahepatic recruitment of CD161+CD8+T cells was mainly CD161<jats:sup>hi<\/jats:sup>CD8+T cell subpopulation, which has a weak antiviral response, but increased pro\u2010inflammatory effect, suggesting that CD161 may serve as a potential marker of liver\u2010damaging T cells.<\/jats:p><\/jats:sec>","DOI":"10.1002\/iid3.70118","type":"journal-article","created":{"date-parts":[[2025,1,12]],"date-time":"2025-01-12T17:54:05Z","timestamp":1736704445000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Intrahepatic CD161<sup>hi<\/sup>CD8+T Cell Recruitment Has a Pathogenetic Potential in Chronic HBV Infection"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-8619-7469","authenticated-orcid":false,"given":"Jianfei","family":"Li","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory the Second Affiliated Hospital of Anhui Medical University Hefei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qian","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory the Second Affiliated Hospital of Anhui Medical University Hefei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wanlu","family":"Duan","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory the Second Affiliated Hospital of Anhui Medical University Hefei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi","family":"Duan","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory the Second Affiliated Hospital of 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