慢性乙型肝炎患者HBeAg特异性T细胞应答与血清HBeAg 滴度变化的关系研究

目的 分析慢性乙型肝炎（CHB）患者抗病毒治疗前后HBeAg特异性T细胞应答与血浆HBeAg 滴度动态变化有无关系.方法 分别收集22例CHB患者抗病毒治疗前、治疗后3、6、12月的外周血共88份标本,以HBeAg蛋白刺激外周血单个核细胞,采用酶联免疫斑点技术（ELISPOT）检测产生IFN-γ的HBeAg特异性T细胞的频率,并检测患者HBV DNA、HBsAg、HBeAg等病毒学指标.结果 患者抗病毒治疗前和治疗后3、6、12月总的T细胞反应阳性率分别为31.8%（7/22）、50.0%（11/22）、77.3%（17/22）和95.5%（21/22）;治疗后12月T细胞反应频率明显高于治疗前和治疗后3月,差异有统计学意义（P〈0.05）;核苷类似物治疗组与干扰素治疗组治疗后T细胞反应频率比较,差异无统计学意义（P〉0.05）.患者治疗后12月T细胞的平均反应强度明显高于治疗前、治疗后3月及治疗后6月,差异有统计学意义（P〈0.05）,核苷类似物治疗组与干扰素治疗组均分别得出上述相同的结果.患者T细胞的平均反应强度与血浆HBeAg COI无相关性（r=-0.107,P=0.319）.结论 CHB患者抗病毒治疗后HBeAg特异性T细胞的应答较治疗前有所增强,但这种变化与血浆HBeAg 滴度的动态变化无明显相关性.

The relationship between HBeAg specific T cell immune responses and titer of serum HBeAg in chronic hepatitis B patients

Objective To analyze the correlation between HBeAg specific T cell immune responses and titer of serum HBeAg in chronic hepatitis B patients accepting antiviral therapy. Methods 22 patients of chronic hepatitis B（CHB） accepting antiviral thera- py were included in this study. The peripheral blood monocular cells（PBMCs） were separated from the whole blood collected before treatment and three months, six months and twelve months after treatment, respectively. ELISPOT assay was used to detect the fre- quency and strength of secreting IFN-7 cells of PBMCs stimulated by HBeAg protein. HBV DNA, HBsAg, HBeAg in serum were detected at the same time. Results The frequency of T cell responses in patients to HBV specific proteins were 31.8% （7/22）, 50.0%（11/22） ,77. 3% （17/22） and 95.5% （21/22） at the time of before treatment and three months, six months and twelve months after antiviral therapy, respectively. The frequency of HBeAg specific T cell responses in patients at twelve months after treatment were significantly higher than those of before and three months after treatment and responses in patients at six months after treatment were significantly higher than those of before treatment（P〈0.05）. The strength of HBeAg specific T cell responses was expressed as spot forming cells（SFCs） per 2 × 10^5 input cells. The SFCs of T cell responses in patients twelve months after treatment were significant higher than those of patients before treatment and three months and six months after treatment（P〈0.05）. There was no significant correlation between SFCs of T cell responses to HBeAg with titer of HBeAg in serum,P〉0.05. Conclusion The HBeAg specific T cell responses in chronic hepatitis B patients after treatment is higher than that before treat- ment,but there is no significant correlation between SFCs of T cell responses to HBeAg with titer of HBeAg in serum.