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

• Published in: Science (American Association for the Advancement of Science) 2010-07, Vol.329 (5987), p.85-89
• Main Authors: Li, Peng, Burke, Shannon, Wang, Juexuan, Chen, Xiongfeng, Ortiz, Mariaestela, Lee, Song-Choon, Lu, Dong, Campos, Lia, Goulding, David, Ng, Bee Ling, Dougan, Gordon, Huntly, Brian, Gottgens, Bertie, Jenkins, Nancy A, Copeland, Neal G, Colucci, Francesco, Liu, Pentao
• Format: Article
• Language: English
• Subjects: Animals; Beta cells; Biological and medical sciences; Cell differentiation, maturation, development, hematopoiesis; Cell Line, Tumor; Cell Lineage; Cell lines; Cell physiology; Cells; Cells, Cultured; Cellular biology; Coculture Techniques; Cytotoxicity, Immunologic; Fundamental and applied biological sciences. Psychology; Gene Deletion; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Developmental; Gene Knock-In Techniques; Genes, T-Cell Receptor beta; Killer Cells, Natural - cytology; Killer Cells, Natural - immunology; Killer Cells, Natural - physiology; Lymphocytes; Lymphopoiesis - genetics; Melanoma, Experimental - immunology; Melanoma, Experimental - therapy; Mice; Mice, Inbred C57BL; Mice, Knockout; Molecular and cellular biology; Natural killer cells; Oligonucleotide Array Sequence Analysis; Precursor Cells, T-Lymphoid - cytology; Precursor Cells, T-Lymphoid - physiology; Receptors, Antigen, T-Cell, alpha-beta - metabolism; Repressor Proteins - genetics; Repressor Proteins - metabolism; Signal Transduction; Stem cells; Stromal cells; Stromal Cells - cytology; Stromal Cells - physiology; T lymphocytes; T-Lymphocytes - cytology; T-Lymphocytes - immunology; T-Lymphocytes - physiology; T-Lymphocytes - transplantation; Tamoxifen - analogs & derivatives; Tamoxifen - pharmacology; Thymocytes; Tissue therapy; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism; Tumors
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1188063

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.