Murine induced pluripotent stem cells  can be derived from and differentiate  into natural killer T cells.
NKT cells demonstrate antitumor activity when activated to produce Th1 cytokines by DCs loaded with alpha-galactosylceramide, the prototypic NKT cell-activating glycolipid antigen. However, most patients do not have sufficient numbers of NKT cells to induce an effective immune response in this context, indicating a need for a source of NKT cells that could be used to supplement the endogenous cell population. Induced pluripotent stem cells (iPSCs) hold tremendous potential for cell-replacement therapy, but whether it is possible to generate functionally competent NKT cells from iPSCs has not been rigorously assessed. In this study, we successfully derived iPSCs both from embryonic fibroblasts from mice harboring functional NKT cell-specific rearranged T cell receptor loci in the germline and from splenic NKT cells from WT adult mice. These iPSCs could be differentiated into NKT cells in vitro and secreted large amounts of the Th1 cytokine IFN-gamma. Importantly, iPSC-derived NKT cells recapitulated the known adjuvant effects of natural NKT cells and suppressed tumor growth in vivo. These studies demonstrate the feasibility of expanding functionally competent NKT cells via an iPSC phase, an approach that may be adapted for NKT cell-targeted therapy in humans.
Watarai
Hiroshi
H
RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa 230-0045, Japan.
Fujii
Shin-ichiro
S
Yamada
Daisuke
D
Rybouchkin
Andrei
A
Sakata
Sakura
S
Nagata
Yuko
Y
Iida-Kobayashi
Midori
M
Sekine-Kondo
Etsuko
E
Shimizu
Kanako
K
Shozaki
Yohei
Y
Sharif
Jafar
J
Matsuda
Masashi
M
Mochiduki
Shinobu
S
Hasegawa
Takanori
T
Kitahara
Genta
G
Endo
Takaho A
TA
Toyoda
Tetsuro
T
Ohara
Osamu
O
Harigaya
Ken-ichi
K
Koseki
Haruhiko
H
Taniguchi
Masaru
M
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000276:immunology / Q000494:pharmacology; D005699:Galactosylceramides / Q000276:immunology / Q000494:pharmacology; D006017:Glycolipids / Q000276:immunology / Q000494:pharmacology; D057026:Induced Pluripotent Stem Cells; D051379:Mice; D055611:Natural Killer T-Cells / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013154:Spleen / Q000187:drug effects / Q000276:immunology
D016207:Cytokines; D005699:Galactosylceramides; D006017:Glycolipids; D011948:Receptors, Antigen, T-Cell; C493154:alpha-galactosylceramide; C103873:KRN 7000