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

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

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 CD_4^+ 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 CD_4^+ 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 CD_4^+ 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 CD_4^+ T 细胞应答强度分别为(156±105)、(56±68)、(229±114)SFC/10~6PBMC(每10~6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。

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 IFN~/ 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/10^6PBMC （ 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.