In vitro induction of natural killer T cells from embryonic stem cells prepared using somatic cell nuclear transfer.
The ectopic expression of the Notch receptor ligand delta-like 1 on stromal cells allows the induction of T cells from embryonic stem cells (ESCs). However, these in vitro-generated T cells are not transplantable because they are too immature to mount an immune response in an immunocompromised animal. We efficiently generated a subset of T cells called invariant natural killer T (iNKT) cells from ESCs derived from peripheral iNKT cells using somatic cell nuclear transfer (ntESCs). These iNKT cells matured autonomously in vivo and exhibited an adjuvant effect accompanying the production of interferon-gamma in an antigen-specific manner. This adjuvant effect culminated in the inhibition of inoculated tumor cell growth. Our results indicate that ntESC-derived iNKT cells are transplantable lymphocytes that will be beneficial for the induction of immune tolerance and the treatment of autoimmune diseases, tumors, and infections.
Wakao
Hiroshi
H
Department of Environmental Biology, School of Medicine, Hokkaido University, N15W7, Sapporo 060-8638, Japan. hwakao@med.hokudai.ac.jp
Wakao
Rika
R
Sakata
Sakura
S
Iwabuchi
Kazuya
K
Oda
Atsushi
A
Fujita
Hiroyoshi
H
D000818:Animals; D017252:CD3 Complex / Q000235:genetics; D002467:Cell Nucleus / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000235:genetics; D053595:Embryonic Stem Cells / Q000166:cytology / Q000276:immunology*; D050990:GATA3 Transcription Factor / Q000235:genetics; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D009687:Nuclear Proteins / Q000235:genetics; D053652:Nuclear Transfer Techniques; D020395:Receptors, Interleukin-7 / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017252:CD3 Complex; D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; D009687:Nuclear Proteins; C499311:RAG2 protein, human; D020395:Receptors, Interleukin-7