Abstract
During positive selection, thymocytes transition through a stage during which T cell antigen receptor (TCR) signaling controls CD4-versus-CD8 lineage 'choice' and subsequent maturation. Here we describe a previously unknown T cell–specific protein, Themis, that serves a distinct function during this stage. In Themis−/− mice, thymocyte selection was impaired and the number of transitional CD4+CD8int thymocytes as well as CD4+ or CD8+ single-positive thymocytes was lower. Notably, although we detected no overt TCR-proximal signaling deficiencies, Themis−/− CD4+CD8int thymocytes showed developmental defects consistent with attenuated signaling that were reversible by TCR stimulation. Our results identify Themis as a critical component of the T cell developmental program and suggest that Themis functions to sustain and/or integrate signals required for proper lineage commitment and maturation.
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Change history
19 August 2009
NOTE: In the version of this article initially published, citation of the linked articles published in the same issue (ni.1769 and ni.1766) is missing. These should be cited on page 841 at the end of the first paragraph of the Results section. The error has been corrected in the HTML and PDF versions of the article.
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Acknowledgements
We thank A. Grinberg for assistance with gene-targeting experiments and the generation of chimeric mice; A. Singer (National Cancer Institute) for Bcl-2-transgenic and Cd8a−/− mice and anti-TCRβ; J. Kaye (The Scripps Research Institute) for rabbit polyclonal anti-Tox; D. Littman (New York University) for antibody to Runx1 and Runx3; D. El-Khoury for technical assistance; and A. Singer, L. Samelson, B.J. Fowlkes and S. Hayes for critical reading of the manuscript. Supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Cancer Institute, National Institute on Aging, Center for Cancer Research, US National Institutes of Health.
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R.L., S.U. and P.E.L. designed research; R.L., S.U, J.L, K.-D.S., L.L. and J.P. did research; Y.Z. and N.-P.W. did and analyzed microarray experiments; K.F.W., L.W. and R.B. generated GATA-3-transgenic mice and antibodies to ThPOK; and R.L and P.E.L. wrote the paper.
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Lesourne, R., Uehara, S., Lee, J. et al. Themis, a T cell–specific protein important for late thymocyte development. Nat Immunol 10, 840–847 (2009). https://doi.org/10.1038/ni.1768
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DOI: https://doi.org/10.1038/ni.1768
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