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Asymmetric cell division shapes naive and virtual memory T-cell immunity during ageing

Author

Listed:
  • Mariana Borsa

    (ETH Zürich
    University of Oxford)

  • Niculò Barandun

    (ETH Zürich)

  • Fabienne Gräbnitz

    (ETH Zürich)

  • Isabel Barnstorf

    (ETH Zürich)

  • Nicolas S. Baumann

    (ETH Zürich)

  • Katharina Pallmer

    (ETH Zürich)

  • Samira Baumann

    (ETH Zürich)

  • Dominique Stark

    (ETH Zürich)

  • Miroslav Balaz

    (ETH Zürich)

  • Nathalie Oetiker

    (ETH Zürich)

  • Franziska Wagen

    (ETH Zürich)

  • Christian Wolfrum

    (ETH Zürich)

  • Anna Katharina Simon

    (University of Oxford)

  • Nicole Joller

    (University of Zurich)

  • Yves Barral

    (ETH Zürich)

  • Roman Spörri

    (ETH Zürich)

  • Annette Oxenius

    (ETH Zürich)

Abstract

Efficient immune responses rely on heterogeneity, which in CD8+ T cells, amongst other mechanisms, is achieved by asymmetric cell division (ACD). Here we find that ageing, known to negatively impact immune responses, impairs ACD in murine CD8+ T cells, and that this phenotype can be rescued by transient mTOR inhibition. Increased ACD rates in mitotic cells from aged mice restore the expansion and memory potential of their cellular progenies. Further characterization of the composition of CD8+ T cells reveals that virtual memory cells (TVM cells), which accumulate during ageing, have a unique proliferation and metabolic profile, and retain their ability to divide asymmetrically, which correlates with increased memory potential. The opposite is observed for naive CD8+ T cells from aged mice. Our data provide evidence on how ACD modulation contributes to long-term survival and function of T cells during ageing, offering new insights into how the immune system adapts to ageing.

Suggested Citation

  • Mariana Borsa & Niculò Barandun & Fabienne Gräbnitz & Isabel Barnstorf & Nicolas S. Baumann & Katharina Pallmer & Samira Baumann & Dominique Stark & Miroslav Balaz & Nathalie Oetiker & Franziska Wagen, 2021. "Asymmetric cell division shapes naive and virtual memory T-cell immunity during ageing," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22954-y
    DOI: 10.1038/s41467-021-22954-y
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