Reprogramming of T cells to natural killer-like cells upon Bcl11b deletion

Peng Li; Shannon Burke; Juexuan Wang; Xiongfeng Chen; Mariaestela Ortiz; Song Choon Lee; Dong Lu; Lia Campos; David Goulding; Bee Ling Ng; Gordon Dougan; Brian Huntly; Bertie Gottgens; Nancy A. Jenkins; Neal G. Copeland; Francesco Colucci; Pentao Liu

doi:10.1126/science.1188063

Reprogramming of T cells to natural killer-like cells upon Bcl11b deletion

Peng Li, Shannon Burke, Juexuan Wang, Xiongfeng Chen, Mariaestela Ortiz, Song Choon Lee, Dong Lu, Lia Campos, David Goulding, Bee Ling Ng, Gordon Dougan, Brian Huntly, Bertie Gottgens, Nancy A. Jenkins, Neal G. Copeland, Francesco Colucci, Pentao Liu

Research output: Contribution to journal › Article › peer-review

269 Scopus citations

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.

Original language	English (US)
Pages (from-to)	85-89
Number of pages	5
Journal	Science
Volume	329
Issue number	5987
DOIs	https://doi.org/10.1126/science.1188063
State	Published - Jul 2 2010

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title = "Reprogramming of T cells to natural killer-like cells upon Bcl11b deletion",

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.",

author = "Peng Li and Shannon Burke and Juexuan Wang and Xiongfeng Chen and Mariaestela Ortiz and Lee, {Song Choon} and Dong Lu and Lia Campos and David Goulding and Ng, {Bee Ling} and Gordon Dougan and Brian Huntly and Bertie Gottgens and Jenkins, {Nancy A.} and Copeland, {Neal G.} and Francesco Colucci and Pentao Liu",

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T1 - Reprogramming of T cells to natural killer-like cells upon Bcl11b deletion

AU - Li, Peng

AU - Burke, Shannon

AU - Wang, Juexuan

AU - Chen, Xiongfeng

AU - Ortiz, Mariaestela

AU - Lee, Song Choon

AU - Lu, Dong

AU - Campos, Lia

AU - Goulding, David

AU - Ng, Bee Ling

AU - Dougan, Gordon

AU - Huntly, Brian

AU - Gottgens, Bertie

AU - Jenkins, Nancy A.

AU - Copeland, Neal G.

AU - Colucci, Francesco

AU - Liu, Pentao

PY - 2010/7/2

Y1 - 2010/7/2

N2 - 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.

AB - 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.

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Reprogramming of T cells to natural killer-like cells upon Bcl11b deletion

Abstract

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