Frontiers in Immunology | |
Hepatitis B surface antigen reduction is associated with hepatitis B core-specific CD8+ T cell quality | |
Immunology | |
Masayuki Kurosaki1  Shun Kaneko2  Takashi Honda3  Ryotaro Sakamori4  Tetsuo Takehara4  Miyako Murakawa5  Yasuhiro Asahina6  Tatsuya Kanto7  Sachiyo Yoshio7  Masaya Sugiyama8  Shokichi Takahama9  Yuji Masuta9  Hirotomo Murakami1,10  Takuya Yamamoto1,11  Victor Appay1,12  | |
[1] Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan;Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan;Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan;Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan;Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan;Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan;Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan;Department of Liver Disease Control, Tokyo Medical and Dental University, Tokyo, Japan;Department of Liver Diseases, Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Chiba, Japan;Department of Viral Pathogenesis and Controls, National Center for Global Health and Medicine, Tokyo, Japan;Laboratory of Precision Immunology, Center for Intractable Diseases and ImmunoGenomics, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan;Laboratory of Precision Immunology, Center for Intractable Diseases and ImmunoGenomics, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan;Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan;Laboratory of Precision Immunology, Center for Intractable Diseases and ImmunoGenomics, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan;Laboratory of Translational Cancer Immunology and Biology, Next-generation Precision Medicine Research Center, Osaka International Cancer Institute, Osaka, Japan;The Research Institute for Microbial Diseases, Osaka University, Osaka, Japan;Department of Virology and Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan;Laboratory of Precision Immunology, Center for Intractable Diseases and ImmunoGenomics, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan;Université de Bordeaux, CNRS, Institut national de la santé et de la recherche médicale (INSERM), ImmunoConcEpT, UMR 5164, Bordeaux, France; | |
关键词: Chronic hepatitis B; HBsAg; HBV-specific CD8 + T cells; scRNA-seq; cytotoxicity; | |
DOI : 10.3389/fimmu.2023.1257113 | |
received in 2023-07-12, accepted in 2023-09-07, 发布年份 2023 | |
来源: Frontiers | |
【 摘 要 】
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+ T cell responses are essential for managing viral replication, but their effect on HBsAg levels remains unclear. We studied the traits of activated CD8+ T cells and HBV-specific CD8+ T cells in the blood of CHB patients undergoing nucleos(t)ide analog (NUC) therapy. For the transcriptome profiling of activated CD8+ T cells in peripheral blood mononuclear cells (PBMCs), CD69+ CD8+ T cells were sorted from six donors, and single-cell RNA sequencing (scRNA-seq) analysis was performed. To detect HBV-specific CD8+ 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+ 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+ T cells utilized by IFN-γ/TNFα/CD107A/CD137 revealed that HBcore-specific cells exhibited greater polyfunctionality, suggesting that the quality of HBV-specific CD8+ T cells varies among antigens. Moreover, a subset of HBcore-specific CD8+ T cells with lower cytolytic potential was inversely correlated with HBsAg level. Our results revealed a stimulant-dependent qualitative difference in HBV-specific CD8+ T cells in patients with CHB undergoing NUC therapy. Hence, the induction of HBcore-specific CD8+ T cells with lower cytolytic potential could be a new target for reducing HBsAg levels.
【 授权许可】
Unknown
Copyright © 2023 Takahama, Yoshio, Masuta, Murakami, Sakamori, Kaneko, Honda, Murakawa, Sugiyama, Kurosaki, Asahina, Takehara, Appay, Kanto and Yamamoto
【 预 览 】
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