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Science 329 (5987): 85-89

Copyright © 2010 by the American Association for the Advancement of Science

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

Peng Li,1 Shannon Burke,1,2 Juexuan Wang,1 Xiongfeng Chen,4 Mariaestela Ortiz,1,* Song-Choon Lee,1,{dagger} Dong Lu,1 Lia Campos,1 David Goulding,1 Bee Ling Ng,1 Gordon Dougan,1 Brian Huntly,5 Bertie Gottgens,5 Nancy A. Jenkins,6 Neal G. Copeland,6 Francesco Colucci,2,3,{ddagger} Pentao Liu1,§

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, reproduction, 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.

1 Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1HH, UK.
2 Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge CB22 3AT, UK.
3 Centre for Trophoblast Research, Physiology Building, Downing Street, University of Cambridge, Cambridge CB2 3EG, UK.
4 SAIC-Frederick, National Cancer Institute–Frederick, Frederick, MD 21701, USA.
5 Cambridge Institute for Medical Research, Wellcome Trust–MRC Building, Hills Road, Cambridge CB2 0XY, UK.
6 Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos 138673, Singapore.

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

{dagger} Present address: Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos 138673, Singapore.

{ddagger} 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.

§ To whom correspondence should be addressed. E-mail: pl2{at}sanger.ac.uk


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