慢性HBV感染患者抗原表位特异性CTL与ALT水平无关

ALT Level was Independent to Antigen-specific Cytotoxic T Lymphocytes in Patients with Chronic Hepatitis B

【目的】通过定量分析慢性乙型肝炎患者体内乙型肝炎病毒(HBV)特异性的细胞毒性T淋巴细胞,探讨特异性细胞毒性T淋巴细胞水平与血清丙氨酸氨基转移酶水平和病毒复制状态的关系。【方法】从慢性乙型肝炎患者外周血分离外周血单个核细胞(PBMC),用HLA-A2限制的HBcAg抗原表位肽-五聚体复合体及CD8单克隆抗体染色后,用流式细胞仪检测HBV特异性的细胞毒性T淋巴细胞,同时检测患者的肝功能和定量分析HBVDNA。【结果】32例HLA-A2阳性的慢性乙型肝炎患者外周血均可检测到HBV特异性的细胞毒性T淋巴细胞,五聚体阳性细胞占CD8阳性细胞的比例为1.3%±1.1%,统计分析抗原表位特异性细胞毒性T淋巴细胞频率与丙氨酸氨基转移酶水平相关性不显著(r=0.163,P=0.163)。分组对比发现病毒载量低者(HBVDNA定量<105拷贝/mL)抗原表位特异性细胞毒性T淋巴细胞水平(1.96%±1.26%)高于病毒载量高者(0.82%±0.52%,P<0.05)。【结论】慢性乙型肝炎患者外周血中存在抗原表位特异性细胞毒性T淋巴细胞,抗原表位特异性细胞毒性T淋巴细胞可能与控制HBV的复制有关,但主要肝损害并非直接由抗原表位特异性细胞毒性T淋巴细胞引起。

[Objective] To detect HBV antigen specific cytotoxic T lymphocytes （CTL） and study their association with alanine aminotransferase （ALT） and viral replication in chronic hepatitis B patients. [Methods] The frequency of HBcAg -specific CTL cells in the peripheral blood mononuclear cells （PBMC） from 32 patients persistent infection with HBV were quantified by flow cytometry using HLA-A2 restricted HBV peptide pentamers complex（Pro5TM MHC Pentamers）.[Results] The HBcAg-specific CTL cells were detected in all individuals with chronic HBV infection, the average of the frequency of HBcAg-specific CTL cells were 1.3%±1.1%. The frequency of HBcAg-specific CTL had no relationship with level of ALT （r=0.163 ,P=0.163）. The patients with low virus load （HBV DNA 〈 10^5 copies/mL） had more HBV-specific CTL cells （1.96%±1.26%） than the patients with high virus load （0.82%±0.52%, P〈 0.05）. [Conclusions] The patients with chronic HBV infection had HBcAg-specific CTL in peripheral blood. HBcAg-specific CTL may play an important role in inhibiting viral replication of the patients with chronic hepatitis B. But major liver cell damage was not directly caused by antigen-specific CTL.