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β-catenin does not regulate memory T cell phenotype

Nature Medicine volume 16, pages 513–514 (2010)Cite this article

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The Wnt–β-catenin axis constitutes an evolutionarily conserved pathway that is important for hematopoietic stem cell self-renewal capacities and other developmental processes in vivo. In the absence of Wnt-induced signaling, cytoplasmic β-catenin is constitutively phosphorylated by glycogen synthase kinase-3β (GSK-3β) and targeted for degradation by the proteasome. Upon exposure to Wnt ligands, GSK-3β becomes phosphorylated and β-catenin protein accumulates and translocates to the nucleus, where it binds Lef/Tcf family proteins and facilitates transcriptional activation1. Despite evidence that the β-catenin pathway regulates thymocyte development, its function in post-thymic T cells is poorly understood. It was recently suggested by Gattinoni et al.2 that activation of this pathway may arrest effector T cell differentiation and generate CD8+ memory stem cells. These experiments were almost exclusively performed after addition of a GSK-3β inhibitor during T cell priming, and the investigators observed accumulation of an unusual population of activated CD62LhighCD44low cells. Upon adoptive transfer in vivo, those cells showed more potent antitumor capabilities than other subpopulations of activated T cells. A better understanding of the mechanism of this effect could improve immunotherapies for clinical translation. However, in contrast to the results of Gattinoni et al.2, acquired with a pharmacologic inhibitor, we have used a genetic approach and find no evidence that the β-catenin pathway regulates T cell memory phenotype.

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Figure 1: Activation of the Wnt–β-catenin pathway does not generate CD8+ memory stem cells.

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Authors and Affiliations

  1. Department of Pathology, The University of Chicago, Chicago, Illinois, USA

    Gregory Driessens, Yan Zheng & Thomas F Gajewski

  2. Department of Medicine, The University of Chicago, Chicago, Illinois, USA

    Thomas F Gajewski

Authors
  1. Gregory Driessens
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  2. Yan Zheng
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  3. Thomas F Gajewski
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Contributions

G.D. and T.F.G. designed the research; G.D. and Y.Z. performed the research; G.D. and T.F.G. analyzed the data; G.D. and T.F.G. wrote the paper. G.D. is a Fellow of the Leukemia and Lymphoma Society.

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Correspondence to Thomas F Gajewski.

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The authors declare no competing financial interests.

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Driessens, G., Zheng, Y. & Gajewski, T. β-catenin does not regulate memory T cell phenotype. Nat Med 16, 513–514 (2010). https://doi.org/10.1038/nm0510-513

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