並列タイトル等iPS細胞はin vitroデングウイルス感染実験に用いられる樹状細胞の由来として有用である
タイトル(掲載誌)Journal of General Virology
授与機関名Nagasaki University (長崎大学)
一般注記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.
長崎大学学位論文 学位記番号:博(医歯薬)甲第1094号 学位授与年月日:平成30年9月5日
Author: Dao Huy Manh, Shusaku Mizukami, Shyam Prakash Dumre, Muhareva Raekiansyah, Satoru Senju, Yasuharu Nishimura, Juntra Karbwang, Nguyen Tien Huy, Kouichi Morita, Kenji Hirayama
Citation: Journal of General Virology, 99(9), pp.1239-1247; 2018
Nagasaki University (長崎大学), 博士(医学) (2018-09-05)
DOIinfo:doi/10.1099/jgv.0.001119
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