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

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)230-237
Number of pages8
JournalBlood
Volume115
Issue number2
DOIs
Publication statusPublished - 14-01-2010
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Generation of functional NKT cells in vitro from embryonic stem cells bearing rearranged invariant Vα14-Jα18 TCRα gene'. Together they form a unique fingerprint.

Cite this