EB病毒对脐带血树突状细胞分化和功能的影响.pdf

上海交通大学医学院硕士研究生学位论文
胞和 DC。感染 EBV 后,脐带血 DC 吞噬葡聚糖的能力降低;细胞表面
分化和成熟标记与正常对照相比表现为:CD14 分子的下调不明显,而
MHC Ⅱ类分子和协同刺激分子上调不明显,MHCⅠ类分子的表达降低;
细胞因子分泌的改变表现为:LPS 刺激后细胞分泌的 IL-6、IL-10 和 TNF-α
不增高,而 TGF-β1 在 EBV 感染后分泌增高,同时 EBV 还抑制了 IL-12p35
和 IFN-γ的 mRNA 表达。
结论:单核细胞和未成熟 DC 均可被 EBV 感染,并且由于成人外周
血单核细胞和 DC 内 LMP1 蛋白 mRNA 的拷贝数明显高于脐带血单核细
胞和 DC,推测 EBV 在成人外周血单核细胞和未成熟 DC 内更易复制。
EBV 抑制了 DC 的吞噬功能,阻碍了 DC 的分化和成熟,使 DC 摄取处
理抗原和提呈抗原的能力受损。MHC I 类分子的降低导致在控制 EBV
感染中发挥关键性作用的 MHC I 类分子限制性的 CD8+细胞毒性 T 细胞
功能受损。此外,EBV 还使 DC 分泌抑制性细胞因子增加,抑制了宿主
免疫,并且使免疫应答反应向 T 辅助细胞 2 方向偏移,削弱了细胞免疫
功能,以上因素均可导致 EBV 逃逸宿主免疫。

关键词新生儿,脐带血,EB 病毒,树突状细胞,分化,功能
VI
上海交通大学医学院硕士研究生学位论文
THE IFNLUENCE OF EPSTEIN-BARR VIRUS ON THE
DIFFERENTIATION AND FUNCTION OF CORD BLOOD
DENDRITIC CELLS



ABSTRACT


Objective: To investigate the possible immune escape mechanisms of
EBV and to provide the experimental and therotical bases to prevent and
design treatment protocol for EBV infection by detecting the expression of
EBV-encoding proteins, exploring the influence of EBV on endocytosis,
phenotype and cytokines secretion of cord blood dendritic cells. Comparing
the results with that of adult DC, and exploring the differences between them.
Methods: The genes of virus-encoded proteins were tested by
RT-quantitative PCR. The expression of EBV-encoding proteins, endocytosis
of dendritic cells and the expression of differentiation and maturation
markers on dendritic cells were determined by immunofluorescence staining
and flow cytometry. The protein level and mRNA levels of cytokines were
determined by ELISA and RT-quantitative PCR respectively.
Results: The EBV-encoding proteins, early antigen and virus capsid
antigen were expressed on infected cord blood monocytes, so did the mRNA
of latent membrane protein 1 and BcLF-1 in infected monocytes and
dendritic cells. Besides, the copy number of LMP1 gene in adult peripheral
blood monocytes and dendritic cells were higher than that in