Jin Ying-Ying, Wang Xi, Du Jing, Cao Rui-Ming, Law Helen K W, Wang Juan-Juan, Chen Tong-Xin
Department of Allergy and Immunology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.
Department of Pediatrics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
Hum Immunol. 2014 Apr;75(4):306-16. doi: 10.1016/j.humimm.2014.02.002. Epub 2014 Feb 12.
Epstein-Barr virus (EBV) is a tumorigenic virus which has effectively infected nearly all human beings with over 95% adult being seropositive. The persistence of latent EBV infection is not fully understood. Recent studies point towards a hypothesis of immune suppression and immune evasion involving regulatory T cells (Tregs) and dendritic cells (DCs). We sought to explore the mechanism of EBV suppression and immune evasion.
We compared the effects of EBV on cord blood (CB) and adult DCs differentiation and maturation including phenotype by flow cytometry, cytokine by ELISA and RT-PCR. And we evaluated the function of DC by co-culture DC and Treg by detection the expression of Foxp3, the phenotype and the cytokine profile of Tregs by flow cytometry.
CB DCs derived from EBV-infected CB monocytes or from EBV-infected CB immature DCs (iDCs) displayed distinct phenotypes of "semi-mature" DCs with high expression of co-stimulatory molecules, such as CD40, CD80 and CD86 but low cytokine production, related to immune tolerance and homeostasis. While the EBV-infected adult iDCs resemble that of "pathogen-driven regulatory mature DCs" with high expression of co-stimulatory molecules, down-regulation of IL-12 secretion and up-regulation of IL-10 secretion, related to protection of host and immune evasion of pathogens. EBV infected cord blood monocytes-derived DCs drived Tregs development by driving the expression of Foxp3, increasing the expression of CTLA-4, decreasing the expression of GITR and promoted the generation of intracellular IL-2 and IL-10 by Tregs.
Epstein-Barr virus induces the differentiation of semi-mature dendritic cells from cord blood monocytes. The differences between CB and adult DCs suggested that the developmental maturity of the cells may affect their immune responses to EBV infection.
爱泼斯坦-巴尔病毒（EBV）是一种致瘤病毒，几乎有效感染了所有人类，超过95%的成年人血清学呈阳性。潜伏性EBV感染的持续存在尚未完全了解。最近的研究指向了一种涉及调节性T细胞（Tregs）和树突状细胞（DCs）的免疫抑制和免疫逃逸假说。我们试图探索EBV抑制和免疫逃逸的机制。
我们通过流式细胞术比较了EBV对脐血（CB）和成人DCs分化及成熟的影响，包括表型，通过ELISA和RT-PCR检测细胞因子。并且我们通过检测Foxp3的表达、Tregs的表型和细胞因子谱，通过DC与Treg共培养来评估DC的功能。
源自EBV感染的CB单核细胞或源自EBV感染的CB未成熟DCs（iDCs）的CB DCs表现出“半成熟”DCs的独特表型，共刺激分子如CD40、CD80和CD86高表达，但细胞因子产生低，这与免疫耐受和内环境稳定有关。而EBV感染的成人iDCs类似于“病原体驱动的调节性成熟DCs”，共刺激分子高表达，IL-12分泌下调，IL-10分泌上调，这与宿主保护和病原体免疫逃逸有关。EBV感染的脐血单核细胞来源的DCs通过驱动Foxp3的表达、增加CTLA-4的表达、降低GITR的表达来驱动Tregs发育，并促进Tregs产生细胞内IL-2和IL-10。
爱泼斯坦-巴尔病毒诱导脐血单核细胞分化为半成熟树突状细胞。CB和成人DCs之间的差异表明细胞的发育成熟度可能影响它们对EBV感染的免疫反应。
