iPS cell serves as a source of dendritic cells for in vitro dengue virus infection model
iPS cell serves as a source of dendritic cells for in vitro dengue virus infection model
复制标题
DOI：
10.1099/jgv.0.001119
复制
发表时间：
2018-09-01
影响因子：
3.8
通讯作者：
Hirayama, Kenji
中科院分区：
文献类型：
--
作者：
Dao Huy Manh;Mizukami, Shusaku;Hirayama, Kenji
在与免疫反应和疫苗开发有关的登革热研究中，缺乏适当的模型一直是一个严重关切的问题。在登革热病毒（DENV）的体外模型研究中，这仍然是一个障碍，因为它需要足够数量的具有统一特征的树突状细胞（DC）。其他来源的DC，主要是单核细胞来源的DC (moDC)，尽管存在数量、增殖和供体依赖性等局限性，但仍被使用。最近人类iPS细胞的发展具有长期、稳定、功能特征和理想的HLA背景，当然提供了额外的优势。因此，我们假设iPS衍生细胞将是传统dc的可靠替代品，可用于体外DENV系统。为了建立DENV感染和T细胞激活模型，我们使用iPS细胞（HLA-A*24）作为DC源。制备了iPS-ML-DC，并评估了DENV的传染性，以及主要表面标志物的表达和细胞因子的产生潜力。我们的iPS-ML-DC具有与moDC相似的主要DC标记表达，DENV感染效率和细胞因子产生特性。此外，与未感染的iPS-ML-DC相比，DENV感染的iPS-ML-DC显示出在体外激活hla匹配的T细胞（但不是错配的）的能力，ifn - γ (+) CD69(+) T细胞的比例显着高于未感染的iPS-ML-DC。这证实了iPS-ML-DC对抗原特异性T细胞的激活是抗原提呈细胞的功能。综上所述，成熟潜力、DENV感染效率和T细胞活化能力共同表明，iPS-ML-DC是DENV体外研究中一个有吸引力的DC选择。
The lack of an appropriate model has been a serious concern in dengue research pertinent to immune response and vaccine development. It remains a matter of impediment in dengue virus (DENV) studies when it comes to an in vitro model, which requires adequate quantity of dendritic cells (DC) with uniform characters. Other sources of DC, mostly monocyte derived DC (moDC), have been used despite their limitations such as quantity, proliferation, and donor dependent characters. Recent development of human iPS cells with consistent proliferation for long, stable, functional characteristics and desired HLA background has certainly offered added advantages. Therefore, we hypothesised that iPS derived cells would be a reliable alternative to the traditional DCs to be used with an in vitro DENV system. To develop a DENV infection and T cell activation model, we utilised iPS cells (HLA-A*24) as the source of DC. iPS-ML-DC was prepared and DENV infectivity was assessed apart from the major surface markers expression and cytokine production potential. Our iPS-ML-DC had major DC markers expression, DENV infection efficiency and cytokine production properties similar to that of moDC. Moreover, DENV infected iPS-ML-DC demonstrated the ability to activate HLA-matched T cell (but not mismatched) in vitro as evidenced by significantly higher proportion of IFN-gamma(+) CD69(+) T cells compared to non-infected iPS-ML-DC. This affirmed the antigenspecific T cell activation by iPS-ML-DC as a function of antigen presenting cells. To conclude, maturation potential, DENV infection efficiency and T cell activation ability collectively suggest that iPS-ML-DC serves as an attractive option of DC for use in DENV studies in vitro.