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STAT5A antagonizes TOX in CD8+ T cell exhaustion

Nature Reviews Immunology volume 23, page 73 (2023)Cite this article

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T cell exhaustion is a hallmark developmental stage in chronic infections and cancer, in which the proliferative capacities and cytotoxic and effector functions of T cells are gradually lost until they reach a terminally dysfunctional state. This transition is a complex phenomenon that involves different phenotypic stages of T cells, each of which is characterized by different proliferative and cytotoxic potentials, as well as by the upregulation or downregulation of several inhibitory receptors and transcription factors. Among these factors, TOX has a fundamental role in establishing the terminally exhausted phenotype.

In this preprint (not peer reviewed), Beltra et al. used a mouse model of chronic infection with lymphocytic choriomeningitis virus (LCMV) clone 13 to evaluate the molecular circuits that could antagonize TOX-dependent exhaustion in T cells. Combining different sequencing approaches, the authors discovered an antagonistic circuit between STAT5A and TOX, in which overexpression of STAT5A in LCMV-specific CD8+ T cells led to the preferential expansion of intermediate-exhausted T cells (LY108−CD69−) lacking TOX expression, and Stat5a knockout in mice was associated with a significant reduction in the number and frequency of these T cells.

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Original article

  • Beltra, J.-C. et al. Enhanced STAT5a activation rewires exhausted CD8 T cells during chronic stimulation to acquire a hybrid durable effector like state. Preprint at bioRxiv https://doi.org/10.1101/2022.10.03.509766 (2022)

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  1. Preprint Club, University of Oxford, Oxford, UK

    David Arcia-Anaya & Tim Elliott

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  1. David Arcia-Anaya
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  2. Tim Elliott
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Correspondence to David Arcia-Anaya or Tim Elliott.

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Arcia-Anaya, D., Elliott, T. STAT5A antagonizes TOX in CD8+ T cell exhaustion. Nat Rev Immunol 23, 73 (2023). https://doi.org/10.1038/s41577-022-00833-x

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  • DOI: https://doi.org/10.1038/s41577-022-00833-x

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