Article(id=1317885786930918367, tenantId=1146029695717560320, journalId=1316781422847033486, issueId=1317885672153797495, articleNumber=null, orderNo=null, doi=10.12449/JCH260835, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1767542400000, receivedDateStr=2026-01-05, revisedDate=null, revisedDateStr=null, acceptedDate=1772985600000, acceptedDateStr=2026-03-09, onlineDate=1792138056738, onlineDateStr=2026-10-16, pubDate=1787587200000, pubDateStr=2026-08-25, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1792138056738, onlineIssueDateStr=2026-10-16, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1792138056738, creator=13701087609, updateTime=1792138056738, updator=13701087609, issue=Issue{id=1317885672153797495, tenantId=1146029695717560320, journalId=1316781422847033486, year='2026', volume='42', issue='8', pageStart='1745', pageEnd='2000', issueExtLink='null', onlineDate='null', pubDate='1787587200000', pubDateStr='2026-08-25', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=1, specialIssue=null, createTime=1792138029373, creator='13701087609', updateTime=1792138608261, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1317888100290900262, tenantId=1146029695717560320, journalId=1316781422847033486, issueId=1317885672153797495, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1317888100290900263, tenantId=1146029695717560320, journalId=1316781422847033486, issueId=1317885672153797495, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=1980, endPage=1984, ext={EN=ArticleExt(id=1317885787161605088, articleId=1317885786930918367, tenantId=1146029695717560320, journalId=1316781422847033486, language=EN, title=Mechanism of action of T cell senescence in the progression of liver fibrosis to liver cirrhosis in elderly patients with chronic hepatitis B, columnId=1317885737828205560, journalTitle=Journal of Clinical Hepatology, columnName=Review, runingTitle=null, highlight=null, articleAbstract=

Liver fibrosis is a key pathological process in the transition from chronic liver disease to cirrhosis,especially in elderly patients with chronic hepatitis B,and this process is characterized by rapid progression and poor prognosis. T cell function gradually declines with aging,and T cell senescence is recognized as a key immunological mechanism accelerating the progression of liver fibrosis. Current studies have shown that senescent T cells promote the transition from liver fibrosis to liver cirrhosis by altering the liver inflammatory microenvironment,modulating the activity of fibrosis-related cells,and impairing immune surveillance function. This article systematically reviews the molecular mechanisms of T cell senescence and its role in the progression of liver fibrosis in elderly patients with chronic hepatitis B,as well as novel therapeutic approaches targeting immunosenescence with reference to the latest immunological findings and stem cell-based therapeutic strategies,so as to provide theoretical support for precise intervention for such patients.

, authors=Ting Wang, Chengkai Yang, Xu Xu, authorsList=Ting Wang, Chengkai Yang, Xu Xu, authorCompany=null, correspAuthors=Xu Xu, authorNote=null, correspAuthorsNote=null, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, fund=null), CN=ArticleExt(id=1317885790835815395, articleId=1317885786930918367, tenantId=1146029695717560320, journalId=1316781422847033486, language=CN, title=T细胞衰老在老年慢性乙型肝炎患者肝纤维化向肝硬化进展中的作用机制, columnId=1317885739623367674, journalTitle=临床肝胆病杂志, columnName=综述, runingTitle=null, highlight=null, articleAbstract=

肝纤维化是慢性肝病向肝硬化转变的关键病理过程,尤其在老年慢性乙型肝炎患者中,该过程进展迅速且预后较差。随着年龄增长,T细胞功能逐渐衰退,T细胞衰老被认为是加速肝纤维化进展的重要免疫学机制。当前研究表明,衰老T细胞通过改变肝脏炎症微环境、调节纤维化相关细胞活性及削弱免疫监视功能,促进肝纤维化向肝硬化的转化。本文系统综述了T细胞衰老的分子机制及其在老年慢性乙型肝炎肝纤维化进展中的作用,结合最新免疫学发现及干细胞治疗策略,探讨靶向免疫衰老的新型治疗途径,旨在为此类患者的精准干预提供理论支持。

, authors=王婷, 杨成凯, 徐栩, authorsList=王婷, 杨成凯, 徐栩, authorCompany=null, correspAuthors=徐栩, authorNote=

作者贡献声明

王婷负责综述的总体设计,梳理文献及撰写初稿;杨成凯负责机制分析部分的内容深化;徐栩负责全文的学术审校,观点整合并最终定稿;王婷、杨成凯和徐栩共同完成资料核查与文稿修订。

, correspAuthorsNote=
徐栩, (ORCID:0009-0005-1492-4364)
Xu Xu, (ORCID:0009-0005-1492-4364)
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refs=[Reference(id=1317885794749100033, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885786930918367, doi=null, pmid=null, pmcid=null, year=2020, volume=120, issue=null, pageStart=179, pageEnd=186, url=null, language=null, rfNumber=1, rfOrder=0, authorNames=Jia Y H, Ma L Y, Wang Y D, journalName=Mol Immunol, refType=null, unstructuredReference=Jia Y H, Ma L Y, Wang Y D, et al. NLRP3 inflammasome and related cytokines reflect the immune status of patients with HBV-ACLF[J]. Mol Immunol, 2020, 120: 179-186. DOI: 10.1016/j.molimm.2020.01.011., articleTitle=NLRP3 inflammasome and related cytokines reflect the immune status of patients with HBV-ACLF, refAbstract=null), Reference(id=1317885794841374722, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885786930918367, doi=null, pmid=null, pmcid=null, year=2020, volume=69, issue=8, pageStart=1589, pageEnd=1603, url=null, language=null, rfNumber=2, rfOrder=1, authorNames=Zecca A, Barili V, Canetti D, journalName=Cancer Immunol Immunother, refType=null, unstructuredReference=Zecca A, Barili V, Canetti D, et al. Energy metabolism and cell motility defect in NK-cells from patients with hepatocellular carcinoma[J]. Cancer Immunol Immunother, 2020, 69(8): 1589-1603. DOI: 10.1007/s00262-020-02561-4., articleTitle=Energy metabolism and cell motility defect in NK-cells from patients with hepatocellular carcinoma, refAbstract=null), Reference(id=1317885794912677891, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885786930918367, doi=null, pmid=null, pmcid=null, year=2020, volume=2020, issue=null, pageStart=3019378, pageEnd=null, url=null, language=null, rfNumber=3, rfOrder=2, authorNames=Chen Q B, Lai L M, Chi X L, journalName=Mediators Inflamm, refType=null, unstructuredReference=Chen Q B, Lai L M, Chi X L, et al. CD19+CD24hiCD38hi B cell dysfunction in primary biliary cholangitis[J]. Mediators Inflamm, 2020, 2020: 3019378. DOI: 10.1155/2020/3019378., articleTitle=CD19+CD24hiCD38hi B cell dysfunction in primary biliary cholangitis, refAbstract=null), Reference(id=1317885794988175364, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885786930918367, doi=null, pmid=null, pmcid=null, year=2024, volume=117, issue=1, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=4, rfOrder=3, authorNames=Yang X X, Li J W, Ren M L, journalName=J Leukoc Biol, refType=null, unstructuredReference=Yang X X, Li J W, Ren M L, et al. Comprehensive analysis of immune signatures in primary biliary cholangitis and autoimmune hepatitis[J]. J Leukoc Biol, 2024, 117(1): qiae085. DOI: 10.1093/jleuko/qiae085., articleTitle=Comprehensive analysis of immune signatures in primary biliary cholangitis and autoimmune hepatitis, refAbstract=null), Reference(id=1317885795084644357, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885786930918367, doi=null, pmid=null, pmcid=null, year=2024, volume=52, issue=11, pageStart=6269, pageEnd=6284, url=null, language=null, rfNumber=5, rfOrder=4, authorNames=Li B, Xiong W Y, Zuo W, journalName=Nucleic Acids Res, refType=null, unstructuredReference=Li B, Xiong W Y, Zuo W, et al. Proximal telomeric decompaction due to telomere shortening drives FOXC1-dependent myocardial senescence[J]. Nucleic Acids Res, 2024, 52(11): 6269-6284. DOI: 10.1093/nar/gkae274., articleTitle=Proximal telomeric decompaction due to telomere shortening drives FOXC1-dependent myocardial senescence, refAbstract=null), Reference(id=1317885795160141830, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885786930918367, doi=null, pmid=null, pmcid=null, year=2025, volume=207, issue=1, pageStart=80, pageEnd=91, url=null, language=null, rfNumber=6, rfOrder=5, authorNames=Wang M, Guo Z, Zhao S S, journalName=Br J Haematol, refType=null, unstructuredReference=Wang M, Guo Z, Zhao S S, et al. CD49d promotes T-cell senescence in chronic lymphocytic leukaemia[J]. Br J Haematol, 2025, 207(1): 80-91. DOI: 10.1111/bjh.20135., articleTitle=CD49d promotes T-cell senescence in chronic lymphocytic leukaemia, refAbstract=null), Reference(id=1317885795244027911, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885786930918367, doi=null, pmid=null, pmcid=null, year=2020, volume=134, issue=null, pageStart=110887, pageEnd=null, url=null, language=null, rfNumber=7, rfOrder=6, authorNames=Pangrazzi L, Weinberger B, journalName=Exp Gerontol, refType=null, unstructuredReference=Pangrazzi L, Weinberger B. T cells, aging and senescence[J]. Exp Gerontol, 2020, 134: 110887. DOI: 10.1016/j.exger.2020.110887., articleTitle=T cells, aging and senescence, refAbstract=null), Reference(id=1317885795332108296, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885786930918367, doi=null, pmid=null, pmcid=null, year=2024, volume=23, issue=10, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=8, rfOrder=7, authorNames=Slaets H, Veeningen N, de Keizer P L J, journalName=Aging Cell, refType=null, unstructuredReference=Slaets H, Veeningen N, de Keizer P L J, et al. Are immunosenescent T cells really senescent [J]. Aging Cell, 2024, 23(10): e14300. DOI: 10.1111/acel.14300., articleTitle=Are immunosenescent T cells really senescent, refAbstract=null), Reference(id=1317885795424382985, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885786930918367, doi=null, pmid=null, pmcid=null, year=2023, volume=15, issue=24, pageStart=5835, pageEnd=null, url=null, language=null, rfNumber=9, rfOrder=8, authorNames=Kasamatsu T, journalName=Cancers, refType=null, unstructuredReference=Kasamatsu T. Implications of senescent T cells for cancer immunotherapy[J]. Cancers, 2023, 15(24): 5835. DOI: 10.3390/cancers15245835., articleTitle=Implications of senescent T cells for cancer immunotherapy, refAbstract=null), Reference(id=1317885795516657674, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885786930918367, doi=null, pmid=null, pmcid=null, year=2020, volume=20, issue=2, pageStart=97, pageEnd=100, url=null, language=null, rfNumber=10, rfOrder=9, authorNames=Nakagami H, journalName=Geriatr Gerontol Int, refType=null, unstructuredReference=Nakagami H. Cellular senescence and senescence-associated T cells as a potential therapeutic target[J]. Geriatr Gerontol Int, 2020, 20(2): 97-100. DOI: 10.1111/ggi.13851., articleTitle=Cellular senescence and senescence-associated T cells as a potential therapeutic target, refAbstract=null), Reference(id=1317885795579572235, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885786930918367, doi=null, pmid=null, pmcid=null, year=2024, volume=48, issue=5, pageStart=864, pageEnd=881, url=null, language=null, rfNumber=11, rfOrder=10, authorNames=Nga H T, Nguyen T L, Yi H S, journalName=Diabetes Metab J, refType=null, unstructuredReference=Nga H T, Nguyen T L, Yi H S. T-cell senescence in human metabolic diseases[J]. Diabetes Metab J, 2024, 48(5): 864-881. DOI: 10.4093/dmj.2024.0140., articleTitle=T-cell senescence in human metabolic diseases, refAbstract=null), Reference(id=1317885795646681100, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885786930918367, doi=null, pmid=null, pmcid=null, year=2023, volume=316, issue=1, pageStart=160, pageEnd=175, url=null, language=null, rfNumber=12, rfOrder=11, authorNames=Laphanuwat P, Gomes D C O, Akbar A N, journalName=Immunol Rev, refType=null, unstructuredReference=Laphanuwat P, Gomes D C O, Akbar A N. Senescent T cells: Beneficial and detrimental roles[J]. Immunol Rev, 2023, 316(1): 160-175. DOI: 10.1111/imr.13206., articleTitle=Senescent T cells: Beneficial and detrimental roles, refAbstract=null), Reference(id=1317885795713789965, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885786930918367, doi=null, pmid=null, pmcid=null, year=2025, volume=13, issue=5, pageStart=618, pageEnd=632, url=null, language=null, rfNumber=13, rfOrder=12, authorNames=Huang L, Zhang C G, Jiang A M, journalName=Cancer Immunol Res, refType=null, unstructuredReference=Huang L, Zhang C G, Jiang A M, et al. T-cell senescence in the tumor microenvironment[J]. Cancer Immunol Res, 2025, 13(5): 618-632. DOI: 10.1158/2326-6066.CIR-24-0894., articleTitle=T-cell senescence in the tumor microenvironment, refAbstract=null), Reference(id=1317885795797676046, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885786930918367, doi=null, pmid=null, pmcid=null, year=2021, volume=35, issue=10, pageStart=109220, pageEnd=null, url=null, language=null, rfNumber=14, rfOrder=13, authorNames=Mathiasen S L, Gall-Mas L, Pateras I S, journalName=Cell Rep, refType=null, unstructuredReference=Mathiasen S L, Gall-Mas L, Pateras I S, et al. Bacterial genotoxins induce T cell senescence[J]. Cell Rep, 2021, 35(10): 109220. DOI: 10.1016/j.celrep.2021.109220., articleTitle=Bacterial genotoxins induce T cell senescence, refAbstract=null), Reference(id=1317885795864784911, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885786930918367, doi=null, pmid=null, pmcid=null, year=2025, volume=37, issue=3, pageStart=143, pageEnd=152, url=null, language=null, rfNumber=15, rfOrder=14, authorNames=Fukushima Y, Ueno R, Minato N, journalName=Int Immunol, refType=null, unstructuredReference=Fukushima Y, Ueno R, Minato N, et al. Senescence-associated T cells in immunosenescence and diseases[J]. Int Immunol, 2025, 37(3): 143-152. DOI: 10.1093/intimm/dxae056., articleTitle=Senescence-associated T cells in immunosenescence and diseases, refAbstract=null), Reference(id=1317885795961253904, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885786930918367, doi=null, pmid=null, pmcid=null, year=2020, volume=19, issue=12, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=16, rfOrder=15, authorNames=Covre L P, de Maeyer R P H, Gomes D C O, journalName=Aging Cell, refType=null, unstructuredReference=Covre L P, de Maeyer R P H, Gomes D C O, et al. The role of senescent T cells in immunopathology[J]. Aging Cell, 2020, 19(12): e13272. DOI: 10.1111/acel.13272., articleTitle=The role of senescent T cells in immunopathology, refAbstract=null), Reference(id=1317885796032557073, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885786930918367, doi=null, pmid=null, pmcid=null, year=2019, volume=10, issue=3, pageStart=249, pageEnd=null, url=null, language=null, rfNumber=17, rfOrder=16, authorNames=Yi H S, Kim S Y, Kim J T, journalName=Cell Death Dis, refType=null, unstructuredReference=Yi H S, Kim S Y, Kim J T, et al. T-cell senescence contributes to abnormal glucose homeostasis in humans and mice[J]. Cell Death Dis, 2019, 10(3): 249. DOI: 10.1038/s41419-019-1494-4., articleTitle=T-cell senescence contributes to abnormal glucose homeostasis in humans and mice, refAbstract=null), Reference(id=1317885796095471634, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885786930918367, doi=null, pmid=null, pmcid=null, year=2023, volume=14, issue=9, pageStart=618, pageEnd=null, url=null, language=null, rfNumber=18, rfOrder=17, authorNames=Sim B C, Kang Y E, You S K, journalName=Cell Death Dis, refType=null, unstructuredReference=Sim B C, Kang Y E, You S K, et al. Hepatic T-cell senescence and exhaustion are implicated in the progression of fatty liver disease in patients with type 2 diabetes and mouse model with nonalcoholic steatohepatitis[J]. Cell Death Dis, 2023, 14(9): 618. DOI: 10.1038/s41419-023-06146-8., articleTitle=Hepatic T-cell senescence and exhaustion are implicated in the progression of fatty liver disease in patients with type 2 diabetes and mouse model with nonalcoholic steatohepatitis, refAbstract=null), Reference(id=1317885796166774803, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885786930918367, doi=null, pmid=null, pmcid=null, year=2023, volume=12, issue=16, pageStart=2034, pageEnd=null, url=null, language=null, rfNumber=19, rfOrder=18, authorNames=Shive C L, Kowal C M, Desotelle A F, journalName=Cells, refType=null, unstructuredReference=Shive C L, Kowal C M, Desotelle A F, et al. Endotoxemia associated with liver disease correlates with systemic inflammation and T cell exhaustion in hepatitis C virus infection[J]. Cells, 2023, 12(16): 2034. DOI: 10.3390/cells12162034., articleTitle=Endotoxemia associated with liver disease correlates with systemic inflammation and T cell exhaustion in hepatitis C virus infection, refAbstract=null), Reference(id=1317885796246466580, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885786930918367, doi=null, pmid=null, pmcid=null, year=2025, volume=19, issue=6, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=20, rfOrder=19, authorNames=Zhang H Y, Wang X C, Zhang X, journalName=PLoS Negl Trop Dis, refType=null, unstructuredReference=Zhang H Y, Wang X C, Zhang X, et al. Hepatic ferroptosis induced by Clonorchis sinensis exacerbates liver fibrosis[J]. PLoS Negl Trop Dis, 2025, 19(6): e0013164. DOI: 10.1371/journal.pntd.0013164., articleTitle=Hepatic ferroptosis induced by Clonorchis sinensis exacerbates liver fibrosis, refAbstract=null), Reference(id=1317885797945159701, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885786930918367, doi=null, pmid=null, pmcid=null, year=2024, volume=81, issue=2, pageStart=207, pageEnd=217, url=null, language=null, rfNumber=21, rfOrder=20, authorNames=Yashaswini C N, Qin T Y, Bhattacharya D, journalName=J Hepatol, refType=null, unstructuredReference=Yashaswini C N, Qin T Y, Bhattacharya D, et al. Phenotypes and ontogeny of senescent hepatic stellate cells in metabolic dysfunction-associated steatohepatitis[J]. J Hepatol, 2024, 81(2): 207-217. DOI: 10.1016/j.jhep.2024.03.014., articleTitle=Phenotypes and ontogeny of senescent hepatic stellate cells in metabolic dysfunction-associated steatohepatitis, refAbstract=null), Reference(id=1317885798037434390, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885786930918367, doi=null, pmid=null, pmcid=null, year=2022, volume=237, issue=1, pageStart=436, pageEnd=449, url=null, language=null, rfNumber=22, rfOrder=21, authorNames=Ezhilarasan D, journalName=J Cell Physiol, refType=null, unstructuredReference=Ezhilarasan D. Hepatic stellate cells in the injured liver: Perspectives beyond hepatic fibrosis[J]. J Cell Physiol, 2022, 237(1): 436-449. DOI: 10.1002/jcp.30582., articleTitle=Hepatic stellate cells in the injured liver: Perspectives beyond hepatic fibrosis, refAbstract=null), Reference(id=1317885798284898327, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885786930918367, doi=null, pmid=null, pmcid=null, year=2021, volume=13, issue=10, pageStart=2074, pageEnd=null, url=null, language=null, rfNumber=23, rfOrder=22, authorNames=Shrivastava S, Kottilil S, Sherman K E, journalName=Viruses, refType=null, unstructuredReference=Shrivastava S, Kottilil S, Sherman K E, et al. CCR5+ T-cells homed to the liver exhibit inflammatory and profibrogenic signatures in chronic HIV/HCV-coinfected patients[J]. Viruses, 2021, 13(10): 2074. DOI: 10.3390/v13102074., articleTitle=CCR5+ T-cells homed to the liver exhibit inflammatory and profibrogenic signatures in chronic HIV/HCV-coinfected patients, refAbstract=null), Reference(id=1317885798393950232, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885786930918367, doi=null, pmid=null, pmcid=null, year=2025, volume=109, issue=null, pageStart=102783, pageEnd=null, url=null, language=null, rfNumber=24, rfOrder=23, authorNames=Wu J Z, Zhang L, Zhao Z H, journalName=Ageing Res Rev, refType=null, unstructuredReference=Wu J Z, Zhang L, Zhao Z H, et al. Advancing T-cell immunotherapy for cellular senescence and disease: Mechanisms, challenges, and clinical prospects[J]. Ageing Res Rev, 2025, 109: 102783. DOI: 10.1016/j.arr.2025.102783., articleTitle=Advancing T-cell immunotherapy for cellular senescence and disease: Mechanisms, challenges, and clinical prospects, refAbstract=null), Reference(id=1317885798490419225, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885786930918367, doi=null, pmid=null, pmcid=null, year=2025, volume=37, issue=5, pageStart=534, pageEnd=539, url=null, language=null, rfNumber=25, rfOrder=24, authorNames=Chai J Q, Li L Y, Wu Q M, journalName=Eur J Gastroenterol Hepatol, refType=null, unstructuredReference=Chai J Q, Li L Y, Wu Q M, et al. CD96: Immunoregulation and its role and prospect in immunotherapy of primary hepatocellular carcinoma[J]. Eur J Gastroenterol Hepatol, 2025, 37(5): 534-539. DOI: 10.1097/MEG.0000000000002916., articleTitle=CD96: Immunoregulation and its role and prospect in immunotherapy of primary hepatocellular carcinoma, refAbstract=null), Reference(id=1317885798578499610, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885786930918367, doi=null, pmid=null, pmcid=null, year=2025, volume=112, issue=null, pageStart=105533, pageEnd=null, url=null, language=null, rfNumber=26, rfOrder=25, authorNames=Zhang Q S, Wang J N, Yang T L, journalName=eBioMedicine, refType=null, unstructuredReference=Zhang Q S, Wang J N, Yang T L, et al. SHMT2 regulates CD8+ T cell senescence via the reactive oxygen species axis in HIV-1 infected patients on antiretroviral therapy[J]. eBioMedicine, 2025, 112: 105533. DOI: 10.1016/j.ebiom.2024.105533., articleTitle=SHMT2 regulates CD8+ T cell senescence via the reactive oxygen species axis in HIV-1 infected patients on antiretroviral therapy, refAbstract=null), Reference(id=1317885798649802779, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885786930918367, doi=null, pmid=null, pmcid=null, year=2025, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=27, rfOrder=26, authorNames=Turano P S, Akbulut E, Dewald H K, journalName=bioRxiv, refType=null, unstructuredReference=Turano P S, Akbulut E, Dewald H K, et al. Epigenetic mechanisms regulating CD8+ T cell senescence in aging humans[J]. bioRxiv, 2025. DOI: 10.1101/2025.01.17.633634. [Epub ahead of print], articleTitle=Epigenetic mechanisms regulating CD8+ T cell senescence in aging humans, refAbstract=null), Reference(id=1317885798721105948, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885786930918367, doi=null, pmid=null, pmcid=null, year=2025, volume=41, issue=1, pageStart=109, pageEnd=null, url=null, language=null, rfNumber=28, rfOrder=27, authorNames=Wang S, Wang X O, Zheng X Y, journalName=Cell Biol Toxicol, refType=null, unstructuredReference=Wang S, Wang X O, Zheng X Y, et al. NGR-modified curcumin nanovesicles reverse immunotherapy resistance in triple-negative breast cancer via TLR9 and mTOR pathway modulation[J]. Cell Biol Toxicol, 2025, 41(1): 109. DOI: 10.1007/s10565-025-10055-1., articleTitle=NGR-modified curcumin nanovesicles reverse immunotherapy resistance in triple-negative breast cancer via TLR9 and mTOR pathway modulation, refAbstract=null), Reference(id=1317885798796603421, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885786930918367, doi=null, pmid=null, pmcid=null, year=2025, volume=24, issue=5, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=29, rfOrder=28, authorNames=Admasu T D, Yu J S, journalName=Aging Cell, refType=null, unstructuredReference=Admasu T D, Yu J S. Harnessing immune rejuvenation: Advances in overcoming T cell senescence and exhaustion in cancer immunotherapy[J]. Aging Cell, 2025, 24(5): e70055. DOI: 10.1111/acel.70055., articleTitle=Harnessing immune rejuvenation: Advances in overcoming T cell senescence and exhaustion in cancer immunotherapy, refAbstract=null), Reference(id=1317885798876295198, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885786930918367, doi=null, pmid=null, pmcid=null, year=2020, volume=16, issue=5, pageStart=263, pageEnd=275, url=null, language=null, rfNumber=30, rfOrder=29, authorNames=Khosla S, Farr J N, Tchkonia T, journalName=Nat Rev Endocrinol, refType=null, unstructuredReference=Khosla S, Farr J N, Tchkonia T, et al. The role of cellular senescence in ageing and endocrine disease[J]. Nat Rev Endocrinol, 2020, 16(5): 263-275. DOI: 10.1038/s41574-020-0335-y., articleTitle=The role of cellular senescence in ageing and endocrine disease, refAbstract=null), Reference(id=1317885798972764191, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885786930918367, doi=null, pmid=null, pmcid=null, year=2021, volume=22, issue=24, pageStart=13292, pageEnd=null, url=null, language=null, rfNumber=31, rfOrder=30, authorNames=Nazarie Ignat S R, Gharbia S, Hermenean A, journalName=Int J Mol Sci, refType=null, unstructuredReference=Nazarie Ignat S R, Gharbia S, Hermenean A, et al. Regenerative potential of mesenchymal stem cells’ (MSCs) secretome for liver fibrosis therapies[J]. Int J Mol Sci, 2021, 22(24): 13292. DOI: 10.3390/ijms222413292., articleTitle=Regenerative potential of mesenchymal stem cells’ (MSCs) secretome for liver fibrosis therapies, refAbstract=null), Reference(id=1317885799052455968, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885786930918367, doi=null, pmid=null, pmcid=null, year=2025, volume=16, issue=1, pageStart=421, pageEnd=null, url=null, language=null, rfNumber=32, rfOrder=31, authorNames=Bozorgi V, Babaahmadi M, Salehi M, journalName=Stem Cell Res Ther, refType=null, unstructuredReference=Bozorgi V, Babaahmadi M, Salehi M, et al. From signaling pathways to clinical trials: Mesenchymal stem cells as multimodal regenerative architects in liver cirrhosis therapy[J]. Stem Cell Res Ther, 2025, 16(1): 421. DOI: 10.1186/s13287-025-04535-8., articleTitle=From signaling pathways to clinical trials: Mesenchymal stem cells as multimodal regenerative architects in liver cirrhosis therapy, refAbstract=null), Reference(id=1317885799119564833, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885786930918367, doi=null, pmid=null, pmcid=null, year=2021, volume=13, issue=4, pageStart=598, pageEnd=null, url=null, language=null, rfNumber=33, rfOrder=32, authorNames=Janelle V, Delisle J S, journalName=Cancers, refType=null, unstructuredReference=Janelle V, Delisle J S. T-cell dysfunction as a limitation of adoptive immunotherapy: Current concepts and mitigation strategies[J]. Cancers, 2021, 13(4): 598. DOI: 10.3390/cancers13040598., articleTitle=T-cell dysfunction as a limitation of adoptive immunotherapy: Current concepts and mitigation strategies, refAbstract=null), Reference(id=1317885799186673698, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885786930918367, doi=null, pmid=null, pmcid=null, year=2023, volume=14, issue=null, pageStart=1270843, pageEnd=null, url=null, language=null, rfNumber=34, rfOrder=33, authorNames=Calviño C, Ceballos C, Alfonso A, journalName=Front Immunol, refType=null, unstructuredReference=Calviño C, Ceballos C, Alfonso A, et al. Optimization of universal allogeneic CAR-T cells combining CRISPR and transposon-based technologies for treatment of acute myeloid leukemia[J]. Front Immunol, 2023, 14: 1270843. DOI: 10.3389/fimmu.2023.1270843., articleTitle=Optimization of universal allogeneic CAR-T cells combining CRISPR and transposon-based technologies for treatment of acute myeloid leukemia, refAbstract=null), Reference(id=1317885799257976867, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885786930918367, doi=null, pmid=null, pmcid=null, year=2025, volume=18, issue=1, pageStart=81, pageEnd=null, url=null, language=null, rfNumber=35, rfOrder=34, authorNames=Liu Q W, Li J F, Sun X Q, journalName=J Hematol Oncol, refType=null, unstructuredReference=Liu Q W, Li J F, Sun X Q, et al. Immunosenescence and cancer: Molecular hallmarks, tumor microenvironment remodeling, and age-specific immunotherapy challenges[J]. J Hematol Oncol, 2025, 18(1): 81. DOI: 10.1186/s13045-025-01735-w., articleTitle=Immunosenescence and cancer: Molecular hallmarks, tumor microenvironment remodeling, and age-specific immunotherapy challenges, refAbstract=null), Reference(id=1317885799346057252, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885786930918367, doi=null, pmid=null, pmcid=null, year=2021, volume=231, issue=null, pageStart=108830, pageEnd=null, url=null, language=null, rfNumber=36, rfOrder=35, authorNames=Li Y K, Yi J S, Howard J F, journalName=Clin Immunol, refType=null, unstructuredReference=Li Y K, Yi J S, Howard J F, et al. Cellular changes in eculizumab early responders with generalized myasthenia gravis[J]. Clin Immunol, 2021, 231: 108830. DOI: 10.1016/j.clim.2021.108830., articleTitle=Cellular changes in eculizumab early responders with generalized myasthenia gravis, refAbstract=null), Reference(id=1317885799614492709, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885786930918367, doi=null, pmid=null, pmcid=null, year=2022, volume=16, issue=18, pageStart=3333, pageEnd=3351, url=null, language=null, rfNumber=37, rfOrder=36, authorNames=Takasugi M, Yoshida Y, Ohtani N, journalName=Mol Oncol, refType=null, unstructuredReference=Takasugi M, Yoshida Y, Ohtani N. Cellular senescence and the tumour microenvironment[J]. Mol Oncol, 2022, 16(18): 3333-3351. DOI: 10.1002/1878-0261.13268., articleTitle=Cellular senescence and the tumour microenvironment, refAbstract=null), Reference(id=1317885799694184486, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885786930918367, doi=null, pmid=null, pmcid=null, year=2024, volume=8, issue=2, pageStart=72, pageEnd=82, url=null, language=null, rfNumber=38, rfOrder=37, authorNames=Wang X D, Wang J, Peng H D, journalName=Liver Res, refType=null, unstructuredReference=Wang X D, Wang J, Peng H D, et al. Role of immune cell interactions in alcohol-associated liver diseases[J]. Liver Res, 2024, 8(2): 72-82. DOI: 10.1016/j.livres.2024.06.002., articleTitle=Role of immune cell interactions in alcohol-associated liver diseases, refAbstract=null), Reference(id=1317885799799042087, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885786930918367, doi=null, pmid=null, pmcid=null, year=2025, volume=31, issue=2, pageStart=489, pageEnd=508, url=null, language=null, rfNumber=39, rfOrder=38, authorNames=Zeng W F, Liu F R, Liu Y C, journalName=Clin Mol Hepatol, refType=null, unstructuredReference=Zeng W F, Liu F R, Liu Y C, et al. Targeting TM4SF1 promotes tumor senescence enhancing CD8+ T cell cytotoxic function in hepatocellular carcinoma[J]. Clin Mol Hepatol, 2025, 31(2): 489-508. DOI: 10.3350/cmh.2024.0934., articleTitle=Targeting TM4SF1 promotes tumor senescence enhancing CD8+ T cell cytotoxic function in hepatocellular carcinoma, refAbstract=null), Reference(id=1317885799945842728, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885786930918367, doi=null, pmid=null, pmcid=null, year=2021, volume=18, issue=null, pageStart=97, pageEnd=101, url=null, language=null, rfNumber=40, rfOrder=39, authorNames=Sakai Y, Fukunishi S, Takamura M, journalName=Regen Ther, refType=null, unstructuredReference=Sakai Y, Fukunishi S, Takamura M, et al. Clinical trial of autologous adipose tissue-derived regenerative (stem) cells therapy for exploration of its safety and efficacy[J]. Regen Ther, 2021, 18: 97-101. DOI: 10.1016/j.reth.2021.04.003., articleTitle=Clinical trial of autologous adipose tissue-derived regenerative (stem) cells therapy for exploration of its safety and efficacy, refAbstract=null), Reference(id=1317885800012951593, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885786930918367, doi=null, pmid=null, pmcid=null, year=2020, volume=9, issue=3, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=41, rfOrder=40, authorNames=Sakai Y, Fukunishi S, Takamura M, journalName=JMIR Res Protoc, refType=null, unstructuredReference=Sakai Y, Fukunishi S, Takamura M, et al. Regenerative therapy for liver cirrhosis based on intrahepatic arterial infusion of autologous subcutaneous adipose tissue-derived regenerative (stem) cells: Protocol for a confirmatory multicenter uncontrolled clinical trial[J]. JMIR Res Protoc, 2020, 9(3): e17904. 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注:HBV,乙型肝炎病毒;HCV,丙型肝炎病毒;CD28-、CD57+,衰老T细胞标志物表现为共刺激分子CD28的丧失及细胞毒性相关CD57表达增加;PD-1,程序性死亡受体1,在衰老T细胞中表达增加;SASP,衰老相关分泌表型;IL-6,白细胞介素6;IL-17,白细胞介素17;TGF-β,转化生长因子β;TNF-α,肿瘤坏死因子α;HSC,肝星状细胞;ECM,细胞外基质。

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T细胞衰老在老年慢性乙型肝炎患者肝纤维化向肝硬化进展中的作用机制
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王婷 , 杨成凯 , 徐栩
临床肝胆病杂志 | 综述 2026,42(8): 1980-1984
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临床肝胆病杂志 |综述 2026 , 42 (8) : 1980 -1984
T细胞衰老在老年慢性乙型肝炎患者肝纤维化向肝硬化进展中的作用机制
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王婷, 杨成凯, 徐栩
作者信息
  • 昆明医科大学附属甘美医院全科医学科,昆明 650224
通讯作者:
徐栩, (ORCID:0009-0005-1492-4364)
Xu Xu, (ORCID:0009-0005-1492-4364)
作者简介:

作者贡献声明

王婷负责综述的总体设计,梳理文献及撰写初稿;杨成凯负责机制分析部分的内容深化;徐栩负责全文的学术审校,观点整合并最终定稿;王婷、杨成凯和徐栩共同完成资料核查与文稿修订。

Mechanism of action of T cell senescence in the progression of liver fibrosis to liver cirrhosis in elderly patients with chronic hepatitis B
Ting Wang, Chengkai Yang, Xu Xu
Affiliations
  • Department of General Practice,Ganmei Hospital Affiliated to Kunming Medical University,Kunming 650224,China
出版时间: 2026-08-25 doi: 10.12449/JCH260835
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肝纤维化是慢性肝病向肝硬化转变的关键病理过程,尤其在老年慢性乙型肝炎患者中,该过程进展迅速且预后较差。随着年龄增长,T细胞功能逐渐衰退,T细胞衰老被认为是加速肝纤维化进展的重要免疫学机制。当前研究表明,衰老T细胞通过改变肝脏炎症微环境、调节纤维化相关细胞活性及削弱免疫监视功能,促进肝纤维化向肝硬化的转化。本文系统综述了T细胞衰老的分子机制及其在老年慢性乙型肝炎肝纤维化进展中的作用,结合最新免疫学发现及干细胞治疗策略,探讨靶向免疫衰老的新型治疗途径,旨在为此类患者的精准干预提供理论支持。

乙型肝炎,慢性  /  肝纤维化  /  肝硬化  /  T淋巴细胞  /  细胞衰老

Liver fibrosis is a key pathological process in the transition from chronic liver disease to cirrhosis,especially in elderly patients with chronic hepatitis B,and this process is characterized by rapid progression and poor prognosis. T cell function gradually declines with aging,and T cell senescence is recognized as a key immunological mechanism accelerating the progression of liver fibrosis. Current studies have shown that senescent T cells promote the transition from liver fibrosis to liver cirrhosis by altering the liver inflammatory microenvironment,modulating the activity of fibrosis-related cells,and impairing immune surveillance function. This article systematically reviews the molecular mechanisms of T cell senescence and its role in the progression of liver fibrosis in elderly patients with chronic hepatitis B,as well as novel therapeutic approaches targeting immunosenescence with reference to the latest immunological findings and stem cell-based therapeutic strategies,so as to provide theoretical support for precise intervention for such patients.

Hepatitis B,Chronic  /  Hepatic Fibrosis  /  Liver Cirrhosis  /  T-Lymphocytes  /  Cellular Senescence
王婷, 杨成凯, 徐栩. T细胞衰老在老年慢性乙型肝炎患者肝纤维化向肝硬化进展中的作用机制. 临床肝胆病杂志, 2026 , 42 (8) : 1980 -1984 . DOI: 10.12449/JCH260835
Ting Wang, Chengkai Yang, Xu Xu. Mechanism of action of T cell senescence in the progression of liver fibrosis to liver cirrhosis in elderly patients with chronic hepatitis B[J]. Journal of Clinical Hepatology, 2026 , 42 (8) : 1980 -1984 . DOI: 10.12449/JCH260835
肝纤维化及肝硬化是全球范围内慢性肝病的主要致死原因。老年人群因免疫机能减退,在感染乙型肝炎病毒(hepatitis B virus,HBV)或丙型肝炎病毒(hepatitis C virus,HCV)后,肝脏修复能力下降,纤维化进程显著加速且难以逆转[1-2]。T细胞作为免疫应答的核心,其衰老和耗竭状态会导致肝脏炎症失控及免疫监视功能丧失。研究显示,老年患者体内CD4+和CD8+ T细胞亚群发生显著变化,衰老T细胞不仅分泌促炎因子维持慢性炎症环境,还通过细胞间信号网络直接调控肝星状细胞(hepatic stellate cell,HSC)的活化,从而加剧细胞外基质沉积[3-4]。近年来,针对免疫衰老的干预策略备受关注,特别是牙髓干细胞和脐带间充质干细胞等干细胞疗法在逆转纤维化方面展现出潜力[5-6]。本文将系统阐述T细胞衰老在老年慢性乙型肝炎肝纤维化向肝硬化进展中的分子机制,并探讨相关的免疫干预策略。
衰老T细胞的关键特征是表面标志物谱系发生特征性变化,其中最典型的是共刺激分子CD28的丧失以及细胞毒性相关CD57表达增加,呈现效应记忆T细胞的衰老表型[7-8]。这类细胞虽然部分仍具有增殖能力,但总体增殖活性明显下降,细胞因子分泌谱异常,典型的炎症因子如干扰素γ和肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)分泌减少,免疫调节功能受损[8-9]。此外,衰老T细胞的细胞毒性功能减弱,导致对病毒和异常细胞(如肿瘤细胞)的清除能力降低[8]。CD49d在慢性淋巴细胞白血病患者中促进T细胞衰老,表现为免疫抑制表型和免疫功能障碍[6]。衰老T细胞在代谢上表现出异常,如线粒体功能障碍、氧化应激增加,且伴随衰老相关分泌表型(senescence-associated secretory phenotype,SASP)的形成,分泌不同于正常T细胞的促炎因子[9-10]。总体而言,衰老T细胞的表型和功能均发生显著改变,表现为免疫功能下降和促炎状态。
诱导T细胞衰老的因素错综复杂,主要可归结为内在遗传与细胞自主因素以及外在微环境与免疫相关因素两大类。
端粒缩短是细胞衰老的经典标志,T细胞在反复抗原刺激后端粒逐渐缩短,DNA损伤反应被激活,细胞周期抑制因子表达增加,引发细胞周期停滞和衰老[7,11-12]。此外,代谢重编程异常也是加速其衰老的重要机制,衰老T细胞表现出线粒体功能障碍、氧化应激增加及能量代谢紊乱,这些变化与T细胞功能降低密切相关[11,13]。
慢性炎症刺激是关键的外部驱动力。如白细胞介素6(interleukin-6,IL-6)、TNF-α等炎症因子的持续存在会导致T细胞功能障碍。在老年人群中,慢性低度炎症状态(即SASP)维持了炎症微环境,进一步促进T细胞衰老[11]。同时,细菌产生的基因毒素等感染因素也可通过特定信号轴调控SASP并诱导T细胞早衰[14]。综上,内外因素的协同作用共同推进了T细胞的衰老进程。
衰老T细胞通过分泌促炎因子维持SASP,形成免疫微环境的炎症状态[10-11]。这种持续的炎症刺激不仅影响自身功能,还可调节其他免疫细胞功能,如促进巨噬细胞和自然杀伤细胞的功能失衡,导致免疫微环境整体失衡[9,13]。此外,衰老T细胞中免疫检查点信号通路如程序性死亡受体1(programmed cell death 1,PD-1)/程序性死亡受体配体1(programmed cell death-ligand 1,PD-L1)表达增加,进一步抑制免疫应答,促进免疫逃逸[9,15]。衰老T细胞与免疫微环境中的其他细胞形成复杂的交互影响,如与巨噬细胞、调节性T细胞等相互作用,促进慢性炎症和组织损伤[15-16]。免疫衰老不仅导致抗感染能力下降,还与代谢疾病、肿瘤等多种老年相关疾病的发生发展密切相关[7,13]。因此,衰老T细胞在维持和调节免疫微环境的动态平衡中起着关键作用,成为抗衰老和免疫治疗的重要靶点。
衰老T细胞在老年慢性乙型肝炎患者肝纤维化的慢性炎症维持中扮演重要角色。首先,衰老T细胞表现出分泌异常炎症因子的特征,这些因子包括IL-6、TNF-α等促炎细胞因子,通过激活HSC促进纤维化进程的加剧。在糖尿病前期患者中,衰老CD8+ T细胞(CD28-CD57+)的数量增加,这些细胞高度表达促炎细胞因子和细胞毒性分子,且其产生的活性氧水平升高,进一步加剧肝脏的炎症反应及胰岛素抵抗,提示衰老T细胞通过炎症介质维持肝脏的慢性炎症状态[17]。此外,肝巨噬细胞与衰老T细胞之间存在相互作用,增强了促纤维化的信号传导。研究显示,肝巨噬细胞分泌的IL-15能够诱导激活T细胞的旁观者效应,促进肝脏疾病进展[18]。免疫调节失衡是另一个关键因素,衰老T细胞导致抗炎反应减弱,炎症持续存在,造成肝组织的进一步损伤。HCV感染者体内伴有T细胞的耗竭和衰老,其与慢性炎症指标如IL-6、干扰素诱导蛋白10水平呈正相关,且干扰素治疗可以部分逆转该状态,提示T细胞衰老与肝脏慢性炎症紧密关联[19]。因此,衰老T细胞通过分泌促炎因子、免疫调节失衡及与肝巨噬细胞的相互作用,维持肝脏慢性炎症,为肝纤维化的进展创造条件。
衰老T细胞通过分泌特定细胞因子直接促进HSC的活化,进而促进胶原蛋白沉积和肝纤维化进程。细胞因子如转化生长因子β和IL-17被发现在衰老T细胞中上调,这些因子能够激活HSC,加速纤维组织形成[18,20]。在信号通路层面,衰老T细胞通过调节Wnt/β-联蛋白信号通路和核因子κB等关键纤维化信号通路,增强纤维化相关基因的表达。研究表明,肝脏中的衰老T细胞激活核因子κB信号通路,促进肝脏炎症和纤维化相关基因的表达,从而推动肝纤维化进程[18,20]。此外,衰老T细胞通过介导肝脏免疫微环境的改变,促进HSC的增殖和抗凋亡能力。肝纤维化模型中,肝脏免疫微环境的变化导致HSC表现出抗凋亡表型,使其持续存活并分泌大量胶原蛋白,推动纤维化的不可逆进展[21-22]。综上所述,衰老T细胞通过分泌促纤维化细胞因子和调控信号通路,强化HSC的活化状态,促进肝纤维化的发生和发展。
衰老T细胞的免疫监视功能下降是肝纤维化向肝硬化进展的重要机制。随着T细胞衰老,机体对病毒(如HBV、HCV)持续复制的控制能力减弱,导致肝细胞损伤加重,进而推动纤维化持续进展[23]。慢性炎症和纤维化的累积促使肝组织结构发生重塑,最终发展为肝硬化。相关研究显示,肝纤维化患者中衰老T细胞比例升高,与纤维化严重度呈正相关[18]。衰老T细胞介导的免疫失调使得肝纤维化过程不可逆,成为肝硬化形成的关键因素[17-18]。此外,衰老T细胞表达的CC趋化因子受体5等受体促进其向肝脏迁移,积聚在肝组织中,发挥促炎及促纤维化作用,加速肝纤维化向肝硬化转变[23]。因此,衰老T细胞的功能障碍不仅削弱了对病毒的清除能力,还通过持续的促炎和促纤维化机制,驱动肝纤维化向肝硬化发生不可逆的进展(图1)。
自然老化过程中的T细胞衰老主要由端粒缩短和长期的低度炎症引发,表现为CD28缺失以及SASP,这属于一种全局性、非抗原特异性的免疫功能衰退[7,13]。慢性乙型肝炎状态下的T细胞耗竭则是由HBV抗原持续刺激引起,具有高度的病原体特异性,其核心特征是PD-1、T细胞免疫球蛋白黏蛋白分子3等抑制性受体的高表达以及免疫效应功能的阶梯式丧失。自然老化过程中的T细胞衰老与慢性乙型肝炎状态下的T细胞耗竭的深刻联系在于,老年慢性乙型肝炎患者体内呈现这两种病理状态的叠加与交织。衰老导致的全局免疫微环境退化构成了特异性免疫功能耗竭的易感背景,而病毒持续感染造成的耗竭又反向加速了T细胞的全局衰老进程,两者共同塑造了老年慢性乙型肝炎患者的独特免疫状态。
在老年慢性乙型肝炎患者中,T细胞呈现出显著的双重受损特征。具体表现为外周血和肝脏局部不仅存在大量CD28-CD57+的衰老T细胞[17],同时这些细胞表面耗竭标志物的表达丰度显著高于单纯老年人群体或年轻慢性乙型肝炎患者。这种叠加表型导致T细胞的抗原特异性增殖能力和细胞毒性因子的分泌能力降至极低水平,取而代之的是促炎及促纤维化因子的持续、大量释放[18]。
在老年慢性乙型肝炎患者的肝脏微环境中,免疫衰老直接加剧并固化T细胞的耗竭状态。衰老T细胞所维持的SASP改变了肝脏局部的细胞因子网络,持续存在的异常炎症介质阻碍了正常效应T细胞的存活与功能发挥,迫使残存的特异性T细胞加速进入不可逆的耗竭阶段[11]。同时,衰老引发的代谢重编程障碍严重削弱了T细胞响应病原体的能量代谢灵活性,使得处于耗竭状态的T细胞完全丧失自我修复与克隆扩增的能力[7,13]。这种衰老与耗竭的协同演进,最终导致肝脏局部免疫监视屏障彻底崩溃,直接驱动肝纤维化向肝硬化阶段的快速恶化[23]。
当前针对T细胞衰老的干预核心在于延缓免疫功能衰退并重塑肝脏微环境,主要涵盖以下两个方面。(1)免疫调节治疗:通过阻断PD-1/PD-L1等免疫检查点通路,能够逆转T细胞衰退并重新激活其抗病毒与抗纤维化能力[24-25]。同时,使用抗氧化剂及代谢酶调节剂降低细胞内活性氧水平,可有效改善CD8+ T细胞的衰老表型并维持其免疫功能[26-28]。(2)细胞清除与再生治疗:Senolytics类药物靶向诱导衰老细胞凋亡,直接清除衰老T细胞并减轻SASP的免疫抑制作用,从而恢复微环境平衡[29-30]。间充质干细胞及其外泌体凭借强大的免疫调节与促进组织再生能力,在逆转肝硬化模型中展现出确切的抗炎和抗纤维化疗效[31-32]。此外,基因修饰T细胞技术也为直接增强清除肝脏病变细胞的能力提供了新途径[33-34]。
为推动靶向T细胞衰老的临床转化,未来研究需聚焦以下核心领域。(1)分子机制与靶点挖掘:借助单细胞测序等多组学技术,深度解析衰老T细胞在肝纤维化进程中的关键调控通路,为开发精准靶向药物奠定基础[27,35-36];(2)早期预警标志物开发:筛选高灵敏度的衰老相关分子标志物(含特异性细胞周期抑制因子及分泌表型成分),为老年慢性乙型肝炎患者的肝纤维化风险评估与疗效监测提供精准指标[37-38];(3)临床验证与联合方案优化:在老年人群中系统评估现有免疫治疗与干细胞疗法的安全性,探索免疫调节、细胞清除与代谢干预的综合治疗模式,最终实现该患者群体的个体化干预[25,35,39-41]。
T细胞衰老在老年慢性乙型肝炎患者肝纤维化向肝硬化的进展中发挥核心调控作用。衰老T细胞不仅通过维持慢性炎症微环境直接促进HSC活化,还因免疫监视功能减退加速了疾病的恶化。靶向T细胞衰老的免疫调节与细胞重塑治疗展现出巨大潜力,未来仍需进一步解析其多层次分子机制并筛选高灵敏度标志物以优化临床干预方案。跨学科的深度合作将加速精准靶向免疫衰老的临床转化,从而有效改善老年患者的长期预后。

参考文献 引证文献
排序方式:
1
Jia Y H, Ma L Y, Wang Y D, et al. NLRP3 inflammasome and related cytokines reflect the immune status of patients with HBV-ACLF[J]. Mol Immunol, 2020, 120: 179-186. DOI: 10.1016/j.molimm.2020.01.011.
2
Zecca A, Barili V, Canetti D, et al. Energy metabolism and cell motility defect in NK-cells from patients with hepatocellular carcinoma[J]. Cancer Immunol Immunother, 2020, 69(8): 1589-1603. DOI: 10.1007/s00262-020-02561-4.
3
Chen Q B, Lai L M, Chi X L, et al. CD19+CD24hiCD38hi B cell dysfunction in primary biliary cholangitis[J]. Mediators Inflamm, 2020, 2020: 3019378. DOI: 10.1155/2020/3019378.
4
Yang X X, Li J W, Ren M L, et al. Comprehensive analysis of immune signatures in primary biliary cholangitis and autoimmune hepatitis[J]. J Leukoc Biol, 2024, 117(1): qiae085. DOI: 10.1093/jleuko/qiae085.
5
Li B, Xiong W Y, Zuo W, et al. Proximal telomeric decompaction due to telomere shortening drives FOXC1-dependent myocardial senescence[J]. Nucleic Acids Res, 2024, 52(11): 6269-6284. DOI: 10.1093/nar/gkae274.
6
Wang M, Guo Z, Zhao S S, et al. CD49d promotes T-cell senescence in chronic lymphocytic leukaemia[J]. Br J Haematol, 2025, 207(1): 80-91. DOI: 10.1111/bjh.20135.
7
Pangrazzi L, Weinberger B. T cells, aging and senescence[J]. Exp Gerontol, 2020, 134: 110887. DOI: 10.1016/j.exger.2020.110887.
8
Slaets H, Veeningen N, de Keizer P L J, et al. Are immunosenescent T cells really senescent [J]. Aging Cell, 2024, 23(10): e14300. DOI: 10.1111/acel.14300.
9
Kasamatsu T. Implications of senescent T cells for cancer immunotherapy[J]. Cancers, 2023, 15(24): 5835. DOI: 10.3390/cancers15245835.
10
Nakagami H. Cellular senescence and senescence-associated T cells as a potential therapeutic target[J]. Geriatr Gerontol Int, 2020, 20(2): 97-100. DOI: 10.1111/ggi.13851.
11
Nga H T, Nguyen T L, Yi H S. T-cell senescence in human metabolic diseases[J]. Diabetes Metab J, 2024, 48(5): 864-881. DOI: 10.4093/dmj.2024.0140.
12
Laphanuwat P, Gomes D C O, Akbar A N. Senescent T cells: Beneficial and detrimental roles[J]. Immunol Rev, 2023, 316(1): 160-175. DOI: 10.1111/imr.13206.
13
Huang L, Zhang C G, Jiang A M, et al. T-cell senescence in the tumor microenvironment[J]. Cancer Immunol Res, 2025, 13(5): 618-632. DOI: 10.1158/2326-6066.CIR-24-0894.
14
Mathiasen S L, Gall-Mas L, Pateras I S, et al. Bacterial genotoxins induce T cell senescence[J]. Cell Rep, 2021, 35(10): 109220. DOI: 10.1016/j.celrep.2021.109220.
15
Fukushima Y, Ueno R, Minato N, et al. Senescence-associated T cells in immunosenescence and diseases[J]. Int Immunol, 2025, 37(3): 143-152. DOI: 10.1093/intimm/dxae056.
16
Covre L P, de Maeyer R P H, Gomes D C O, et al. The role of senescent T cells in immunopathology[J]. Aging Cell, 2020, 19(12): e13272. DOI: 10.1111/acel.13272.
17
Yi H S, Kim S Y, Kim J T, et al. T-cell senescence contributes to abnormal glucose homeostasis in humans and mice[J]. Cell Death Dis, 2019, 10(3): 249. DOI: 10.1038/s41419-019-1494-4.
18
Sim B C, Kang Y E, You S K, et al. Hepatic T-cell senescence and exhaustion are implicated in the progression of fatty liver disease in patients with type 2 diabetes and mouse model with nonalcoholic steatohepatitis[J]. Cell Death Dis, 2023, 14(9): 618. DOI: 10.1038/s41419-023-06146-8.
19
Shive C L, Kowal C M, Desotelle A F, et al. Endotoxemia associated with liver disease correlates with systemic inflammation and T cell exhaustion in hepatitis C virus infection[J]. Cells, 2023, 12(16): 2034. DOI: 10.3390/cells12162034.
20
Zhang H Y, Wang X C, Zhang X, et al. Hepatic ferroptosis induced by Clonorchis sinensis exacerbates liver fibrosis[J]. PLoS Negl Trop Dis, 2025, 19(6): e0013164. DOI: 10.1371/journal.pntd.0013164.
21
Yashaswini C N, Qin T Y, Bhattacharya D, et al. Phenotypes and ontogeny of senescent hepatic stellate cells in metabolic dysfunction-associated steatohepatitis[J]. J Hepatol, 2024, 81(2): 207-217. DOI: 10.1016/j.jhep.2024.03.014.
22
Ezhilarasan D. Hepatic stellate cells in the injured liver: Perspectives beyond hepatic fibrosis[J]. J Cell Physiol, 2022, 237(1): 436-449. DOI: 10.1002/jcp.30582.
23
Shrivastava S, Kottilil S, Sherman K E, et al. CCR5+ T-cells homed to the liver exhibit inflammatory and profibrogenic signatures in chronic HIV/HCV-coinfected patients[J]. Viruses, 2021, 13(10): 2074. DOI: 10.3390/v13102074.
24
Wu J Z, Zhang L, Zhao Z H, et al. Advancing T-cell immunotherapy for cellular senescence and disease: Mechanisms, challenges, and clinical prospects[J]. Ageing Res Rev, 2025, 109: 102783. DOI: 10.1016/j.arr.2025.102783.
25
Chai J Q, Li L Y, Wu Q M, et al. CD96: Immunoregulation and its role and prospect in immunotherapy of primary hepatocellular carcinoma[J]. Eur J Gastroenterol Hepatol, 2025, 37(5): 534-539. DOI: 10.1097/MEG.0000000000002916.
26
Zhang Q S, Wang J N, Yang T L, et al. SHMT2 regulates CD8+ T cell senescence via the reactive oxygen species axis in HIV-1 infected patients on antiretroviral therapy[J]. eBioMedicine, 2025, 112: 105533. DOI: 10.1016/j.ebiom.2024.105533.
27
Turano P S, Akbulut E, Dewald H K, et al. Epigenetic mechanisms regulating CD8+ T cell senescence in aging humans[J]. bioRxiv, 2025. DOI: 10.1101/2025.01.17.633634. [Epub ahead of print]
28
Wang S, Wang X O, Zheng X Y, et al. NGR-modified curcumin nanovesicles reverse immunotherapy resistance in triple-negative breast cancer via TLR9 and mTOR pathway modulation[J]. Cell Biol Toxicol, 2025, 41(1): 109. DOI: 10.1007/s10565-025-10055-1.
29
Admasu T D, Yu J S. Harnessing immune rejuvenation: Advances in overcoming T cell senescence and exhaustion in cancer immunotherapy[J]. Aging Cell, 2025, 24(5): e70055. DOI: 10.1111/acel.70055.
30
Khosla S, Farr J N, Tchkonia T, et al. The role of cellular senescence in ageing and endocrine disease[J]. Nat Rev Endocrinol, 2020, 16(5): 263-275. DOI: 10.1038/s41574-020-0335-y.
31
Nazarie Ignat S R, Gharbia S, Hermenean A, et al. Regenerative potential of mesenchymal stem cells’ (MSCs) secretome for liver fibrosis therapies[J]. Int J Mol Sci, 2021, 22(24): 13292. DOI: 10.3390/ijms222413292.
32
Bozorgi V, Babaahmadi M, Salehi M, et al. From signaling pathways to clinical trials: Mesenchymal stem cells as multimodal regenerative architects in liver cirrhosis therapy[J]. Stem Cell Res Ther, 2025, 16(1): 421. DOI: 10.1186/s13287-025-04535-8.
33
Janelle V, Delisle J S. T-cell dysfunction as a limitation of adoptive immunotherapy: Current concepts and mitigation strategies[J]. Cancers, 2021, 13(4): 598. DOI: 10.3390/cancers13040598.
34
Calviño C, Ceballos C, Alfonso A, et al. Optimization of universal allogeneic CAR-T cells combining CRISPR and transposon-based technologies for treatment of acute myeloid leukemia[J]. Front Immunol, 2023, 14: 1270843. DOI: 10.3389/fimmu.2023.1270843.
35
Liu Q W, Li J F, Sun X Q, et al. Immunosenescence and cancer: Molecular hallmarks, tumor microenvironment remodeling, and age-specific immunotherapy challenges[J]. J Hematol Oncol, 2025, 18(1): 81. DOI: 10.1186/s13045-025-01735-w.
36
Li Y K, Yi J S, Howard J F, et al. Cellular changes in eculizumab early responders with generalized myasthenia gravis[J]. Clin Immunol, 2021, 231: 108830. DOI: 10.1016/j.clim.2021.108830.
37
Takasugi M, Yoshida Y, Ohtani N. Cellular senescence and the tumour microenvironment[J]. Mol Oncol, 2022, 16(18): 3333-3351. DOI: 10.1002/1878-0261.13268.
38
Wang X D, Wang J, Peng H D, et al. Role of immune cell interactions in alcohol-associated liver diseases[J]. Liver Res, 2024, 8(2): 72-82. DOI: 10.1016/j.livres.2024.06.002.
39
Zeng W F, Liu F R, Liu Y C, et al. Targeting TM4SF1 promotes tumor senescence enhancing CD8+ T cell cytotoxic function in hepatocellular carcinoma[J]. Clin Mol Hepatol, 2025, 31(2): 489-508. DOI: 10.3350/cmh.2024.0934.
40
Sakai Y, Fukunishi S, Takamura M, et al. Clinical trial of autologous adipose tissue-derived regenerative (stem) cells therapy for exploration of its safety and efficacy[J]. Regen Ther, 2021, 18: 97-101. DOI: 10.1016/j.reth.2021.04.003.
41
Sakai Y, Fukunishi S, Takamura M, et al. Regenerative therapy for liver cirrhosis based on intrahepatic arterial infusion of autologous subcutaneous adipose tissue-derived regenerative (stem) cells: Protocol for a confirmatory multicenter uncontrolled clinical trial[J]. JMIR Res Protoc, 2020, 9(3): e17904. DOI: 10.2196/17904.
2026年第42卷第8期
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doi: 10.12449/JCH260835
  • 接收时间:2026-01-05
  • 首发时间:2026-10-16
  • 出版时间:2026-08-25
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  • 收稿日期:2026-01-05
  • 录用日期:2026-03-09
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    昆明医科大学附属甘美医院全科医学科,昆明 650224

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徐栩, (ORCID:0009-0005-1492-4364)
Xu Xu, (ORCID:0009-0005-1492-4364)
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2种不同金属材料的力学参数
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属
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种数
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species
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鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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