In vitro induction of natural killer T cells from embryonic stem cells prepared using somatic cell nuclear transfer

FASEB J. 2008 Jul;22(7):2223-31. doi: 10.1096/fj.07-104687. Epub 2008 Mar 6.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD3 Complex / genetics
  • Cell Nucleus / immunology*
  • DNA-Binding Proteins / genetics
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / immunology*
  • GATA3 Transcription Factor / genetics
  • Humans
  • Killer Cells, Natural / immunology*
  • Nuclear Proteins / genetics
  • Nuclear Transfer Techniques
  • Receptors, Interleukin-7 / genetics
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • CD3 Complex
  • DNA-Binding Proteins
  • GATA3 Transcription Factor
  • Nuclear Proteins
  • RAG2 protein, human
  • Receptors, Interleukin-7