Generation of functional NKT cells in vitro from embryonic stem cells bearing rearranged invariant Vα14-Jα18 TCRα gene

Hiroshi Watarai, Andrei Rybouchkin, Naomi Hongo, Yuko Nagata, Sakura Sakata, Etsuko Sekine, Nyambayar Dashtsoodol, Takuya Tashiro, Shin Ichiro Fujii, Kanako Shimizu, Kenji Mori, Kyoko Masuda, Hiroshi Kawamoto, Haruhiko Koseki, Masaru Taniguchi

研究成果: Article査読

31 被引用数 (Scopus)

抄録

Establishment of a system with efficient generation of natural killer T (NKT) cells from embryonic stem (ES) cells would enable us to identify the cells with NKTcell potential and obtain NKT cells with desired function. Here, using cloned ES (NKT-ES) cells generated by the transfer of nuclei from mature NKT cells, we have established a culture system that preferentially developed functional NKT cells and also identified early NKT progenitors, which first appeared on day 11 as a c-kit+ population in the cocultures on OP9 cells with expression of Notch ligand, deltalike1 (OP9/Dll-1) and became c-kitlo/- on day 14. Interestingly, in the presence of Notch signals, NKT-ES cells differentiated only to thymic CD44lo CD24hi NKT cells producing mainly interleukin-4 (IL-4), whereas NKT cells resembling CD44hi CD24loliver NKT cells producing mainly interferon γ (IFN-γ) and exhibiting strong adjuvant activity in vivo were developed in the switch culture starting at day 14 in the absence of Notch. The cloned ES culture system offers a new opportunity for the elucidation of the molecular events on NKT-cell development and for the establishment of NKT-cell therapy.

本文言語English
ページ(範囲)230-237
ページ数8
ジャーナルBlood
115
2
DOI
出版ステータスPublished - 14-01-2010
外部発表はい

All Science Journal Classification (ASJC) codes

  • 生化学
  • 免疫学
  • 血液学
  • 細胞生物学

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