不同亚群CD8＋T细胞细胞毒作用对慢性乙型肝炎的影响

目的观察慢性乙型肝炎不同分期及干扰素-a（interferon-a,IFN-a）治疗前后外周血不同亚群CD8＋T细胞细胞毒作用的变化,探讨其在慢性乙型肝炎发病机理及抗病毒治疗中的作用。方法采集20例慢乙肝免疫耐受期患者和20例免疫清除期患者IFN—a治疗前后的外周全血,采用流式细胞仪检测CD8^high和CD8^lowT细胞的颗粒酶B（Granzyme B,GrB）和溶酶体相关膜蛋白-1（Lysosome—associated membrane protein．1,LAMP-1,CD107a）表达变化,并进行分析。结果（1）慢乙肝患者免疫清除期不同亚群CD8＋T细胞GrB和CD107a的表达水平均高于免疫耐受期;（2）不同分期慢乙肝患者CD8^lowT细胞GrB和CD107a的表达水平均高于CD8^highT细胞;（3）IFN—a治疗后CD8^highT细胞的GrB和CD107a表达水平和治疗前相比具有升高趋势,而CD8^lowT细胞反而具有下降趋势;（4）不同亚群CD8＋T细胞的GrB和CD107a表达水平与HBV—DNA载量在免疫耐受期呈正相关,而在免疫清除期呈负相关。结论（1）不同亚群CD8＋T细胞的GrB和CD107a分子在慢乙肝疾病进程及抗病毒治疗中均起重要作用,CD8^lowT细胞的细胞毒作用强于CD8^highT细胞,而CD8^highT细胞的细胞毒效应在IFN—a治疗过程中逐渐增强。（2）不同亚群CD8＋T细胞的GrB和CD107a分子水平与HBV病毒载量的相关性在一定程度上可以提示机体免疫应答与病毒之间的关系。

The cytotoxic effect of CD8+ T subsets plays an important role in the chronic hepatitis B

Objective The aim of this study is to explore the cytotoxic effect of CD8+ T subsets in peripheral blood with chronic hepatitis B subjects who are at immune tolerance phase and immune clearance phase (before and after three months' treatment with interferon-α), further to investigate their impact in the pathogenesis of chronic hepatitis B and antiviral therapy. Methods The subjects of chronic hepatitis B,including 20 subjects of immune tolerance phase and 20 subjects of immune clearance phase, are enrolled in the study. And we use flow cytometry to detect Lysosome-associated membrane protein-1 (LAMP-1,CD107a) and Granzyme B (GrB) expression of CD8high and CD8lowT cells in peripheral blood with chronic hepatitis B subjects. Results (1) At immune clearance phase, the CD8 + T subsets expressing GrB and CD107a are higher than counterpart of immune tolerance phase. (2) At immune tolerance phase and immune clearance phase in HBV infection, the CD8lowT cells expressing GrB and CD107a are higher than that of CD8highT cells. (3) After three months' treatment with interferon-α, except for GrB+ CD107a+CD8highT cells, CD8highT cells expressing GrB and CD107a present a tendency of ascensus at the same time with that of CD8lowT cells a tendency of descensus except for GrB-CD107a+ CD8lowT cells. (4) The CD8 +Tcell expressing GrB and CD107a, correlate positively with HBV DNA load at immune tolerance phase, but correlated negatively at immune clearance phase. Conclusions (1) GrB and CD107a molecule expressed by different CD8 + T cell subsets play an important role in disease evolution and antivirus therapy of chronic hepatitis B, the cytotoxic effect of CD8highT cell subset became more and more stronger during the treatment of IFN-α, and the cytotoxic effect of CD8lowT cell subset couldn' t be neglected before antivirus therapy. (2)To some degree, the correlation between HBV-DNA load and the expression of GrB and CD107a at different CD8 +T cell subsets, could hint the relationship between virus and immune response.