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The β-catenin–TCF-1 pathway ensures CD4+CD8+ thymocyte survival

Nature Immunology volume 2, pages 691–697 (2001)Cite this article

Abstract

The association of trans-acting T cell factors (TCFs) or lymphoid enhancer factor 1 (LEF-1) with their coactivator β-catenin mediates transient transcriptional responses to extracellular Wnt signals. We show here that T cell maturation depends on the presence of the β-catenin–binding domain in TCF-1. This domain is necessary to mediate the survival of immature CD4+CD8+ double-positive (DP) thymocytes. Accelerated spontaneous thymocyte death in the absence of TCF-1 correlates with aberrantly low expression of the anti-apoptotic protein Bcl-xL. Increasing anti-apoptotic effectors in thymocytes by the use of a Bcl-2 transgene rescued TCF-1–deficient DP thymocytes from apoptosis. Thus, TCF-1, upon association with β-catenin, transiently ensures the survival of immature T cells, which enables them to generate and edit T cell receptor (TCR) α chains and attempt TCR-mediated positive selection.

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Figure 1: TCF-1 isoforms, domains and Tg mice.
Figure 2: Comparable abundance of p45 and p33 isoforms in Tg mice.
Figure 3: The β-catenin domain in TCF-1 was required for T cell maturation.
Figure 4: Cell division among TCF-1–deficient thymocyte subsets.
Figure 5: Spontaneous apoptosis in the absence of TCF-1: restoration in p45-Tg mice.
Figure 6: The absence of TCF-1 did not affect Bcl-2 expression.
Figure 7: Immunoblot analysis of Bcl-2 family proteins in TCF-1–deficient thymocytes.
Figure 8: Enforced Bcl-2 expression in TCF-1–deficient mice restored thymocyte survival.

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Acknowledgements

We thank P. Zaech for expert cell sorting; F. Radtke for primers; B. Kunz for assembling the transgene constructs; A. Strasser and A. Wilson for suggestions and advice; and H. R. MacDonald and J.-C. Cerottini for critical reading of the manuscript. Supported in part by a grant from the Swiss National Science Foundation (to W. H).

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Authors and Affiliations

  1. Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, 155 Ch. des Boveresses, Epalinges, 1066, Switzerland

    Vassilios Ioannidis & Werner Held

  2. Swiss Institute for Experimental, Cancer Research (ISREC), 155 Ch. des Boveresses, Epalinges, 1066, Switzerland

    Friedrich Beermann

  3. Department of Immunology, University Hospital, Heidelberglaan 100, CX, 3584, Utrecht, The Netherlands

    Hans Clevers

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  1. Vassilios Ioannidis
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Correspondence to Werner Held.

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Ioannidis, V., Beermann, F., Clevers, H. et al. The β-catenin–TCF-1 pathway ensures CD4+CD8+ thymocyte survival. Nat Immunol 2, 691–697 (2001). https://doi.org/10.1038/90623

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