摘要
目的 比较分析慢性乙型肝炎及HBV相关肝硬化和肝细胞癌患者间的HBV特异性CD8^(+)T细胞反应活性。方法 选取124例慢乙肝、36例HBV相关肝硬化和114例HBV相关肝细胞癌患者,采用独创的ELISPOT系统定量检测患者外周血中具有反应活性的HBV特异性CD8^(+)T细胞数量;另对19例慢乙肝患者和20例肝细胞癌患者进行纵向追踪(每3~5月检测1次)。结果 慢乙肝组的HBV特异性CD8^(+)T细反应活性与肝硬化组无统计学差异,但明显低于肝细胞癌组,尤其是HBsAg、HBpol和HBe/cAg抗原特异性T细胞。慢乙肝组中,ALT和AST水平正常组、低病毒载量组比ALT和AST水平异常组、高病毒载量组都呈现更高的HBV特异性CD8^(+)T细胞反应活性。NUCs治疗的时间长短对慢乙肝患者HBV特异性T细胞的功能恢复有一定影响,但在相同时长内药物种类对其影响较弱。肝硬化组中,HBeAg阳性组的HBV特异性CD8^(+)T细胞反应活性明显高于HBeAg阴性组(P=0.03)。肝细胞癌组中,AFP正常和DCP正常组的HBV特异性CD8^(+)T细胞反应活性明显高于AFP和DCP异常组。纵向研究结果显示,慢乙肝患者使用NUCs治疗期间,HBV特异性CD8^(+)T细胞反应活性呈逐渐上升趋势;而肝细胞癌患者在靶向药物联合免疫治疗期间,HBV特异性CD8^(+)T细胞反应活性呈现明显上升。结论 HBV特异性CD8^(+)T细胞反应活性在慢乙肝、肝硬化和肝细胞癌的进程中存在差异,且受到病毒学指标、肿瘤标志物以及药物治疗的影响,因此在临床治疗中应密切关注HBV特异性CD8^(+)T细胞反应活性的变化。
This study was performed to investigate the features of HBV-specific CD8^(+)T cell reactivity in patients with chronic hepatitis B(CHB),HBV-induced liver cirrhosis(LC)or hepatocellular carcinoma(HCC).A total of 124 CHB patients,36 LC patients,and 114 HCC patients were enrolled in this study.The reactive HBV-specific CD8^(+)T cells in peripheral blood were enumerated using an innovative ELISPOT system.In addition,19 CHB patients and 20 HCC patients were longitudinally monitored with an interval of 3-5 months.Data showed that the numbers of reactive HBV-specific CD8+T cells in CHB group were not significantly different from that in LC group,but obviously lower than that in HCC group(P=0.0099),especially HBsAg-,HBpol-and HBe/cAg-specific CD8^(+)T cells.In CHB group,the patients with normal ALT level,AST level,or low HBV-DNA load showed significantly more reactive HBV-specific CD8^(+)T cells than the patients with abnormal ALT level,abnormal AST level,or high HBV-DNA load.Furthermore,the duration of NUCs treatment had an impact on the HBV-specific CD8^(+)T cell reactivity in CHB patients,while different NUCs at the same treatment duration did not bring different reactivity of HBV-specific T cells.In LC group,the HBeAg-positive patients presented much more reactive HBV-specific CD8^(+)T cells than the HBeAg-negative patients did.In HCC group,the numbers of reactive HBV-specific CD8^(+)T cells in the patients with normal AFP level or normal DCP level were significantly higher than that in the patients with abnormal AFP level or abnormal DCP level.Longitudinal monitoring results showed that HBV-specific CD8^(+)T cell reactivity displayed a slow upward trend in the CHB patients undergoing NUCs treatment,and an obvious increasing in the HCC patients undergoing combined treatment of targeted drugs and immunotherapy.Taken together,the features of HBV-specific CD8^(+)T cell reactivity are distinct among the CHB,LC and HCC patients,and are influenced by virological indicators,tumor markers and treatment regimens.Therefore,more attention should be paid to the changes of HBV-specific CD8^(+)T cell reactivity during clinical treatment.
作者
朱梦莹
纪瑞雪
李品青
马于琪
焦大敏
岳芳平
吴燕丹
邱洁
傅熙玲
常家宝
ZHU Mengying;JI Ruixue;LI Pinqing;MA Yuqi;JIAO Damin;YUE Fangping;WU Yandan;QIU Jie;FU Xiling;CHANG Jiabao(Department of Liver Disease,Nanjing Second Hospital,Nanjing 210003,China;Department of Microbiology and Immunology,Southeast University Medical School,Nanjing 210009,China;Department of Oncology and Vascular Intervention,Nanjing Second Hospital,Nanjing 210003,China)
出处
《免疫学杂志》
CAS
CSCD
2024年第4期365-374,共10页
Immunological Journal
基金
江苏省卫健委医学科研基金(M2020088)。
关键词
慢性乙型肝炎
肝硬化
肝细胞癌
抗原特异性T细胞检测
Chronic hepatitis B
Cirrhosis
Hepatocellular carcinoma
Antigen-specific T cell detection
