乙型肝炎病毒感染临床转归与宿主细胞免疫的相关性研究

目的 比较慢性乙型肝炎患者、HBV携带者、HBV既往无症状感染者之间T细胞亚群和HBV特异性CD4+ T细胞应答强度的差异,分析宿主的细胞免疫状态对HBV感染后临床转归的影响,探讨乙型肝炎的发病机制,为慢性乙型肝炎的治疗提供新的线索.方法 选取2004年2-10月在北京协和医院肝炎门诊就诊的慢性乙型肝炎患者30例、HBV携带者22例、HBV既往无症状感染者9例以及正常对照11例,使用流式细胞仪检测其T细胞亚群,使用酶联免疫斑点法检测病毒特异性CD4+T细胞应答强度,分析其差异及临床意义.结果 慢性乙型肝炎组CD4+T细胞计数显著低于HBV既往无症状感染组和正常对照组;慢性乙型肝炎组、HBV携带者组、HBV既往无症状感染组病毒特异性CD4+ T细胞应答强度分别为(156±105)、(56±68)、(229±114)SFC/106PBMC(每106个外周血单个核细胞中斑点形成细胞的个数);慢性乙型肝炎组明显高于HBV携带者组(P＜0.01),而低于HBV既往无症状感染组(P＜0.05).结论 慢性乙型肝炎患者、HBV携带者、HBV既往无症状感染者病毒特异性T细胞应答强度存在差异,这种差异可能是造成HBV感染后不同临床转归的主要因素之一.

The relationship between clinical outcomes of hepatitis B virus infection and the host' s cellular immunity

OBJECTIVE: To investigate the differences of peripheral blood T-lymphocyte subsets and the frequencies of HBV-specific CD4 T cells in patients with symptomatic chronic hepatitis B, asymptomatic HBV carriers and patients who had recovered from subclinical HBV infection, to analyze the relationship between different clinical outcomes after HBV infection and the host's cellular immunity and to give a new clue to the treatment of chronic hepatitis B. METHODS: Flow cytometry was used to detect the peripheral blood T-lymphocyte subsets in 30 patients with symptomatic chronic hepatitis B, 22 asymptomatic HBV carriers, 9 patients who had recovered from subclinical HBV infection and 11 healthy blood donors. The frequencies of HBV-specific CD4+ T cells in relation to recombinant HBV core antigen were tested with IFNgamma enzyme-linked immunospot assays (ELISpot). RESULTS: Compared with patients who had recovered from subclinical HBV infection and normal controls, the count of CD4+ T cells decreased in patients with symptomatic chronic hepatitis B. The frequencies of HBV-specific CD4+ T cells were (156 +/- 105), (56 +/- 68) and (229 +/- 114) SFC/10(6)PBMC (SFC: spot-forming cells; PBMC: peripheral blood mononuclear cells) respectively in patients with symptomatic chronic hepatitis B, asymptomatic HBV carriers and patients who had recovered from subclinical HBV infection. The frequencies of HBV-specific CD4+ T cells in patients with symptomatic chronic hepatitis B were markedly higher than those in asymptomatic HBV carriers (P < 0.01), but lower than that in patients who had recovered from subclinical HBV infection (P < 0.05). CONCLUSION: There was significant difference in the frequencies of HBV-specific T cells in patients with symptomatic chronic hepatitis B, asymptomatic HBV carriers and patients who had recovered from subclinical HBV infection and these might be one of the primary reasons for the different clinical outcomes after HBV infection.