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J Gen Virol. 2018 Sep;99(9):1239-1247. doi: 10.1099/jgv.0.001119. Epub 2018 Jul 30.

iPS cell serves as a source of dendritic cells for in vitro dengue virus infection model.

Author information

1
1​Department of Immunogenetics, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, Japan.
2
2​Nagasaki University Graduate School of Biomedical Sciences Doctoral Leadership Program, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
3
3​Department of Clinical Product Development, NEKKEN, Nagasaki University, Nagasaki, Japan.
4
4​Department of Virology, NEKKEN, Nagasaki University, Nagasaki, Japan.
5
5​Department of Immunogenetics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.

Abstract

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-γ+ CD69+ T cells compared to non-infected iPS-ML-DC. This affirmed the antigen-specific 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.

KEYWORDS:

antigen presentation; cellular immunity; dendritic cell; dengue virus; iPS cell; in vitro model

PMID:
30058991
DOI:
10.1099/jgv.0.001119

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