中文摘要：

目的 动态观察急性乙型肝炎（AHB）患者外周血HBcAg18-27表位特异性细胞毒性T淋巴细胞（CTL）、血清ALT、HBV DNA、HBsAg和淋巴细胞亚群的变化,探讨HBV特异性CTL频率的消长在病毒清除以及肝脏损伤中的作用.方法 分别选取AHB、慢性乙型肝炎（CHB）患者外周血,根据人类白细胞抗原（HLA）-A0201结果分为两组：HLA-A0201阳性患者作为HBV特异性CTL检测组、HLA-A0201阴性患者作为特异性抗原表位对照组.用HLA-A0201限制性表位HBcAg18-27五聚体复合物通过流式细胞技术,动态定量检测外周血中HBV特异性CTL频率和T、B淋巴细胞与自然杀伤细胞（NK）和NKT淋巴细胞;以速率法检测血清ALT水平;荧光定量PCR检测HBV DNA水平; Abbott微粒子化学发光技术检测HBV血清学标志物.计量资料采用均数±标准差（（x）±s）表示或中位数（P25-P75）描述,组间比较采用方差分析或非参数检验（KruskalWallis检验和Mann-Whitney U检验）;两种计量指标的关系采用Pearson相关分析.结果 AHB患者入院第1、2、3周外周血HBcAg表位特异性CTL频率分别为2.11%（0.20%～3.64%）、3.56%（1.05%～5.91%）、2.03%（0.33%～3.58%）,高于入院第4、5、6周的0.99%（0.12%～2.16%）、0.29%（0.05%～0.76%）、0.39%（0.05%～0.46%）,也显著高于CHB的0.11%（0.06%～0.29%）,z值分别为-3.258,-4.041,-3.259,P值均＜0.01.AHB患者HBcAg表位特异性CTL峰值延迟于血清HBV DNA、HBsAg和ALT等指标的峰值;在AHB患者中,HBcAg表位特异性CTL高频率患者的血清HBsAg消失时间早于CTL频率较低的患者[（1.75±1.04）周与（4.33±3.51）周,t=-2.018,P＜0.05].CD3＋CD8＋T淋巴细胞频率的峰值出现在入院后第2周,并与HBcAg表位特异性CTL峰值相重叠,两者动态变化规律呈相关性（r=0.420,P＜0.01）.AHB患者早期外周血NK、NKT淋巴细胞数量显著低于正常对照组和CHB患者,但随着病情好转而逐渐恢复,AHB患者外周血NK细胞数量变化与HBc

英文摘要：

Objective This report aims to investigate the dynamical changes of HBcAg18-27 epitope specific cytotoxic T lymphocytes（CTL）, alanine aminotransferase （ALT）, HBV DNA and HBsAg in peripheral blood of acute hepatitis B patients, and to explore the roles of HBcAg18-27-specific CTLs in virus clearance and liver injury. Methods Acute hepatitis B （AHB） and chronic hepatitis B （CHB） patients were divided into two groups according to results of HLA-A0201. Patients with positive HLA-A0201 were classified into HBcAg-specific CTL group and those with negative HLA-A0201 were referred as control group.The specific CTLs were stained with HLA-A0201 limited HBcAg18-27 epitope MHC-Pentamer and the frequencies of CTLs, T, B, NK and NKT cells were detected by flow cytometry （FCM）. The serum ALT, HBV DNA and HBsAg were examined using speed analysis, quantitative PCR and abbott chemiluminescent technology. Results The frequencies of HBcAg18-27-specific CTLs in AHB patients were higher in the early three weeks as compared to the late three weeks. The apex time of HBV-specific CTL frequencies lagged behind those of HBV DNA, HBsAg and ALT. The loss of HBsAg in patients with high frequencies of HBVspecific CTL was earlier than that in patients with low frequencies （t = 2.018, P 〈 0.05）. In the second week the peak frequencies of CD3＋CD8＋ cells overlapped with that of HBcAg18-27-specific CTLs and with a positive correlation between （r = 0.420, P 〈 0.05）. During the early stages of AHB, the frequencies of NK and NKT cells were found significantly lower than that of control group and CHB group and the levels were back to normal after recovery. Moreover, a negative correlation existed between the frequencies of NK cells and the dynamic changes of HBcAg18-27-specific CTLs （r = -0.435, P 〈 0.01） in AHB group. The frequencies of HBcAg18-27-specific CTLs were significantly higher as compared to CHB group in the first three weeks （z = -3.258, -4.04, and -3.259, P 〈 0.01）. Conclusion The early loss of