聚乙二醇化干扰素α-2a治疗慢性乙型肝炎患者免疫细胞B7-H1表达的特点及其临床意义

目的 探讨慢性乙型肝炎患者在接受聚乙二醇化干扰素(PEG-IFN)α-2a治疗后免疫细胞B7-H1表达的变化特点及其临床意义.方法 采用流式细胞术检测14例慢性乙型肝炎患者在PEG-IFNα-2a治疗过程中外周血髓样树突细胞(mDCs)和CD4+T淋巴细胞上B7-H1表达的动态变化情况.体外培养慢性乙型肝炎患者外周血单核细胞,采用酶联免疫斑点法检测分泌干扰素(IFN)γ的T淋巴细胞频数.结果 PEG-IFNα-2a治疗24周,有效组和无效组外周血mDCs的B7-H1阳性表达率分别为10.37%±2.83%和19.27%±4.04%;有效组和无效组CD4+T淋巴细胞的B7-H1阳性表达率分别为19.71%±5.18%和40.43%±7.37%,有效组mDCs和CD4+T淋巴细胞上B7-H1的表达率明显低于无效组.有效组患者治疗前和治疗后每1×105个淋巴细胞可检测到分泌IFNγ的斑点数量分别为(113.33±31.41)个和(266.67±42.26)个,患者治疗后分泌IFNγ的T淋巴细胞频数明显高于治疗前;无效组患者治疗前和治疗后分泌IFNγ的斑点数量分别为(109.87±40.81)个和(55.63±10.27)个,治疗后分泌IFNγ的T淋巴细胞频数与治疗前相比,明显降低.阻断B7-H1途径可明显提高分泌IFNγ的抗原特异性T淋巴细胞频数.结论 接受PEG-IFNα-2a治疗的慢性乙型肝炎患者的疗效与其免疫细胞87-H1的表达有关,阻断B7-H1途径可提高机体清除病毒的特异性T淋巴细胞的免疫功能.

Dynamic changes of B7-H1 expression on mDCs and T cells in chronic hepatitis B patients treated with PEG-IFN alpha-2a

OBJECTIVE: To study the dynamic changes of B7-H1 expression on myeloid dendritic cells (mDCs) and T cells in chronic hepatitis B (CHB) patients undergoing PEG-IFN alpha-2a therapy, and to analyze the association of the changes with the efficiency of interferon-alpha therapy. METHODS: Expressions of B7-H1 on mDCs and T cells in 14 patients with chronic HBV infection, including 6 responders and 8 non-responders to the antiviral therapy, were monitored by using flow cytometric analysis. Peripheral blood mononuclear cells from patients were incubated in vitro and the numbers of IFN-gamma-producing antigen-specific T cells were measured using ELISPOT assay. RESULTS: B7-H1 expressions by mDCs, CD4+ T cells and CD8+ T cells were all significantly upregulated at 4 weeks after starting PEG-IFN alpha-2a therapy. After this time point, B7-H1 expressions persistently decreased in the responders to the antiviral treatment, while non-responders maintained high levels of B7-H1 expression. In addition, the frequency of HBV-specific IFN-gamma-producing T cells significantly increased in the responders, but significantly decreased in the non-responders. Blocking the B7-H1 signal pathway increased the numbers of HBV-specific IFN-gamma-producing T cells in both the responders and non-responders. CONCLUSION: Dynamic changes of B7-H1 expression by mDCs and T cells in CHB patients undergoing PEG-IFN alpha-2a therapy can predict the efficiency of the therapy. Blocking the B7-H1 inhibitory pathway likely enhances the antiviral cellular T-cell responses.