{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T02:58:26Z","timestamp":1780714706496,"version":"3.54.1"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T00:00:00Z","timestamp":1697587200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Despite treatment, hepatitis B surface antigen (HBsAg) persists in patients with chronic hepatitis B (CHB), suggesting the likely presence of the virus in the body. CD8<jats:sup>+<\/jats:sup> T cell responses are essential for managing viral replication, but their effect on HBsAg levels remains unclear. We studied the traits of activated CD8<jats:sup>+<\/jats:sup> T cells and HBV-specific CD8<jats:sup>+<\/jats:sup> T cells in the blood of CHB patients undergoing nucleos(t)ide analog (NUC) therapy. For the transcriptome profiling of activated CD8<jats:sup>+<\/jats:sup> T cells in peripheral blood mononuclear cells (PBMCs), CD69<jats:sup>+<\/jats:sup> CD8<jats:sup>+<\/jats:sup> T cells were sorted from six donors, and single-cell RNA sequencing (scRNA-seq) analysis was performed. To detect HBV-specific CD8<jats:sup>+<\/jats:sup> T cells, we stimulated PBMCs from 26 donors with overlapping peptides covering the HBs, HBcore, and HBpol regions of genotype A\/B\/C viruses, cultured for 10 days, and analyzed via multicolor flow cytometry. scRNA-seq data revealed that CD8<jats:sup>+<\/jats:sup> T cell clusters harboring the transcripts involved in the cytolytic functions were frequently observed in donors with high HBsAg levels. Polyfunctional analysis of HBV-specific CD8<jats:sup>+<\/jats:sup> T cells utilized by IFN-\u03b3\/TNF\u03b1\/CD107A\/CD137 revealed that HBcore-specific cells exhibited greater polyfunctionality, suggesting that the quality of HBV-specific CD8<jats:sup>+<\/jats:sup> T cells varies among antigens. Moreover, a subset of HBcore-specific CD8<jats:sup>+<\/jats:sup> T cells with lower cytolytic potential was inversely correlated with HBsAg level. Our results revealed a stimulant-dependent qualitative difference in HBV-specific CD8<jats:sup>+<\/jats:sup> T cells in patients with CHB undergoing NUC therapy. Hence, the induction of HBcore-specific CD8<jats:sup>+<\/jats:sup> T cells with lower cytolytic potential could be a new target for reducing HBsAg levels.<\/jats:p>","DOI":"10.3389\/fimmu.2023.1257113","type":"journal-article","created":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T08:58:09Z","timestamp":1697619489000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Hepatitis B surface antigen reduction is associated with hepatitis B core-specific CD8+ T cell 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