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Science Signaling  06 Jul 2010:
Vol. 3, Issue 129, pp. ec205
DOI: 10.1126/scisignal.3129ec205

T cells develop in the thymus, where they proceed through several developmental stages, losing alternative lineage potential as they progress. The molecular regulation of this developmental process, however, is not fully understood (see the Perspective by Di Santo). P. Li et al., L. Li et al., and Ikawa et al. now identify expression of the zinc finger transcription factor Bcl11b as the earliest checkpoint in T cell development in mice. Genetic deletion of Bcl11b in developing T cells inhibited commitment to the T cell lineage. Under conditions that should have stimulated T lineage differentiation, Bcl11b-deficient T cell progenitors failed to up-regulate genes associated with lineage-committed T cells and maintained stem cell and progenitor cell–associated gene expression. In both developing and committed T cells, loss of Bcl11b resulted in the generation of cells that resembled natural killer (NK) cells in both phenotype and function. These NK-like cells could be expanded easily in vitro and possessed antitumor cytotoxicity, but they did not exhibit cytotoxicity against normal cells and were not tumorigenic. Because T cells are much easier to obtain from human patients than NK cells, deletion of Bcl11b in T cells may thus provide a source of easy-to-grow NK cells for cell-based antitumor therapies.

P. Li, S. Burke, J. Wang, X. Chen, M. Ortiz, S.-C. Lee, D. Lu, L. Campos, D. Goulding, B. L. Ng, G. Dougan, B. Huntly, B. Gottgens, N. A. Jenkins, N. G. Copeland, F. Colucci, P. Liu, Reprogramming of T cells to natural killer–like cells upon Bcl11b deletion. Science 329, 85–89 (2010). [Abstract] [Full Text]

L. Li, M. Leid, E. V. Rothenberg, An early T cell lineage commitment checkpoint dependent on the transcription factor Bcl11b. Science 329, 89–93 (2010). [Abstract] [Full Text]

T. Ikawa, S. Hirose, K. Masuda, K. Kakugawa, R. Satoh, A. Shibano-Satoh, R. Kominami, Y. Katsura, H. Kawamoto, An essential developmental checkpoint for production of the T cell lineage. Science 329, 93–96 (2010). [Abstract] [Full Text]

J. P. Di Santo, A guardian of T cell fate. Science 329, 44–45 (2010). [Summary] [Full Text]