Published Online June 10 2010
< Science Express Index
Science DOI: 10.1126/science.1188063
  • Report

Reprogramming of T Cells to Natural Killer–Like Cells upon Bcl11b Deletion

  1. Peng Li1,
  2. Shannon Burke1,2,
  3. Juexuan Wang1,
  4. Xiongfeng Chen4,
  5. Mariaestela Ortiz1,*,
  6. Song-Choon Lee1,†,
  7. Dong Lu1,
  8. Lia Campos1,
  9. David Goulding1,
  10. Bee Ling Ng1,
  11. Gordon Dougan1,
  12. Brian Huntly5,
  13. Bertie Gottgens5,
  14. Nancy A. Jenkins6,
  15. Neal G. Copeland6,
  16. Francesco Colucci2,3,‡ and
  17. Pentao Liu1,§
  1. 1Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1HH, UK.
  2. 2Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge, CB22 3AT, UK.
  3. 3Centre for Trophoblast Research, Physiology Building, Downing Street, University of Cambridge, Cambridge, CB2 3EG, UK.
  4. 4SAIC-Frederick, National Cancer Institute–Frederick, Frederick, MD 21701, USA.
  5. 5Cambridge Institute for Medical Research, Wellcome Trust/MRC Building, Hills Road, Cambridge, CB2 0XY, UK.
  6. 6Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore 138673, Singapore.
  1. §To whom correspondence should be addressed. E-mail: pl2{at}sanger.ac.uk

  • ↵* Present address: The Anne McLaren Laboratory for Regenerative Medicine, Cambridge University, Robison Way, Cambridge, CB2 0SZ, UK.

  • ↵† Present address: Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore 138673, Singapore.

  • ↵‡ Present address: Department of Obstetrics and Gynaecology, University of Cambridge Clinical School, Cambridge, CB2 0SW, UK; National Institute for Health Research Cambridge Centre for Biomedical Research, Cambridge, CB2 0QQ, UK.

Abstract

T cells develop in the thymus and are critical for adaptive immunity. Natural killer (NK) lymphocytes constitute an essential component of the innate immune system in tumor surveillance and defense against microbes and viruses. Here, we show that the transcription factor Bcl11b was expressed in all T cell compartments and was indispensable for T-lineage development. When Bcl11b was deleted, T cells from all developmental stages acquired NK cell properties and concomitantly lost or decreased T cell–associated gene expression. These induced T-to-natural-killer (ITNK) cells, which were morphologically and genetically similar to conventional NK cells, killed tumor cells in vitro and effectively prevented tumor metastasis in vivo. Therefore, ITNKs may represent a new cell source for cell-based therapies.

  • Received for publication 8 February 2010.
  • Accepted for publication 20 April 2010.