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Themis, a T cell–specific protein important for late thymocyte development

Nature Immunology volume 10, pages 840–847 (2009)Cite this article

An Erratum to this article was published on 01 January 2010

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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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Figure 1: Structure and expression of E430004N04Rik (Themis).
Figure 2: Development of SP thymocytes is impaired in Themis−/− mice.
Figure 3: Positive and negative selection are impaired in Themis−/− mice.
Figure 4: The generation of CD4+CD8int thymocytes is impaired in Themis−/− mice.
Figure 5: Evidence of a signaling defect in Themis−/− thymocytes at the CD4+CD8int stage.
Figure 6: Expression of GATA-3 and ThPOK is lower in Themis−/− CD69+ CD4SP thymocytes.
Figure 7: GATA-3 and ThPOK are induced in Themis−/− thymocytes by strong TCR signals.
Figure 8: Forced expression of ThPOK or GATA-3 does not restore CD4SP development in Themis−/− mice.
Figure 9: Evidence of a survival defect in CD8SP thymocytes.

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  • 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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Authors and Affiliations

  1. Laboratory of Mammalian Genes and Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland, USA

    Renaud Lesourne, Shoji Uehara, Jan Lee, Ki-Duk Song, LiQi Li, Julia Pinkhasov & Paul E Love

  2. DNA Array Unit, Intramural Research Program, Bethesda, Maryland, USA

    Yongqing Zhang

  3. Laboratory of Immunology, National Institute on Aging, Bethesda, Maryland, USA

    Nan-Ping Weng

  4. Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA

    Kathryn F Wildt, Lie Wang & Remy Bosselut

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Contributions

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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Correspondence to Paul E Love.

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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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