{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T06:18:33Z","timestamp":1785565113815,"version":"3.56.0"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2021,12,26]],"date-time":"2021-12-26T00:00:00Z","timestamp":1640476800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2021,12,26]],"date-time":"2021-12-26T00:00:00Z","timestamp":1640476800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2022,3]]},"abstract":"Abstract<\/jats:title>\n \n Background and Aims<\/jats:title>\n \n Classical CD8 T cells are implicated for protective and pathogenic roles in chronic hepatitis B (CHB) infection. Recently, a subset of CD8 T cells expressing C\u2010X\u2010C chemokine receptor type 5 (CXCR5) and exhibiting features of T\n FH<\/jats:sub>\n cells has been identified during chronic viral infections. However, in CHB, knowledge of their roles is limited.\n <\/jats:p>\n <\/jats:sec>\n \n Approach and Results<\/jats:title>\n \n We characterized circulating CD8\n +<\/jats:sup>\n CXCR5\n +\/\u2212<\/jats:sup>\n cells and investigated their association with clinical and viral factors. We found that CHB infection did not influence the overall frequencies of CD8\n +<\/jats:sup>\n CXCR5\n +<\/jats:sup>\n cells whereas CD8\n +<\/jats:sup>\n CXCR5\n \u2212<\/jats:sup>\n cells were increased. However, among CHB, CD8\n +<\/jats:sup>\n CXCR5\n +<\/jats:sup>\n cells were higher in patients with low HBsAg and HBV\u2010DNA levels, patients who were HBeAg negative and had high fibrosis scores, and these cells exhibited a significant association with HBsAg and HBV\u2010DNA reduction. Contrarily, CD8\n +<\/jats:sup>\n CXCR5\n \u2212<\/jats:sup>\n cells were expanded and positively correlated with patients having high HBsAg, HBV\u2010DNA, and alanine aminotransferase levels. CD8\n +<\/jats:sup>\n CXCR5\n +<\/jats:sup>\n cells express costimulatory molecules ICOS, OX40, CD40 ligand, inhibitory molecule programmed death 1, transcription factors B\u2010cell lymphoma (BCL)\u20102, BCL\u20106, and signal transducer and activator of transcription 3, and are enriched in effector and central memory phenotype. Moreover, these cells are heterogeneous in nature given that they constitute different subsets of cytotoxic follicular T cells (TCF), including TCF1, TCF2, TCF17, and TCF22. Despite expressing high PD\u20101, CD8\n +<\/jats:sup>\n CXCR5\n +<\/jats:sup>\n cells are activated, proliferating, secreting more IFN\u2010\u03b3, IL\u201021, and IL\u201022, and have better cytolytic potential than CD8\n +<\/jats:sup>\n CXCR5\n \u2212<\/jats:sup>\n cells, which were inhibited after PD\u20101\/PD\u2010L1 blockade. CD8\n +<\/jats:sup>\n CXCR5\n +<\/jats:sup>\n cells are efficient in helping B cells in terms of plasmablasts and plasma cell generation.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n In conclusion, CD8\n +<\/jats:sup>\n CXCR5\n +<\/jats:sup>\n cells are enriched in effector phenotypes, produce HBV\u2010specific cytokines despite increased PD\u20101, and are associated with HBsAg and HBV\u2010DNA reduction. These cells competently support B\u2010cell function, required for viral clearance, which may serve as potential therapeutic targets for CHB.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/hep.32210","type":"journal-article","created":{"date-parts":[[2021,10,24]],"date-time":"2021-10-24T09:25:02Z","timestamp":1635067502000},"page":"690-708","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":24,"title":["Programmed death 1 expressing CD8+CXCR5+ follicular T cells constitute effector rather than exhaustive phenotype in patients with chronic hepatitis B"],"prefix":"10.1097","volume":"75","author":[{"given":"Arshi","family":"Khanam","sequence":"first","affiliation":[{"name":"Division of Clinical Care and Research,Institute of Human Virology,University of Maryland School of Medicine,Baltimore,Maryland,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydia S. Y.","family":"Tang","sequence":"additional","affiliation":[{"name":"Division of Clinical Care and Research,Institute of Human Virology,University of Maryland School of Medicine,Baltimore,Maryland,USA"},{"name":"Program in Oncology, Marlene and Stewart Greenebaum Comprehensive Cancer Center,University of Maryland,Baltimore,Maryland,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shyam","family":"Kottilil","sequence":"additional","affiliation":[{"name":"Division of Clinical Care and Research,Institute of Human Virology,University of Maryland School of Medicine,Baltimore,Maryland,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2021,12,26]]},"reference":[{"key":"hep32210-bib-0001-20250824","doi-asserted-by":"crossref","first-page":"2940","DOI":"10.1128\/JVI.02415-06","article-title":"The level of viral antigen presented by hepatocytes influences CD8 T\u2010cell 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