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

Mariana Borsa, Niculò Barandun, Fabienne Gräbnitz, Isabel Barnstorf, Nicolas S. Baumann, Katharina Pallmer, Samira Baumann, Dominique Stark, Miroslav Balaz, Nathalie Oetiker, Franziska Wagen, Christian Wolfrum, Anna Katharina Simon, Nicole Joller, Yves Barral, Roman Spörri and Annette Oxenius ()
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Mariana Borsa: ETH Zürich
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

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: 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.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22954-y

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DOI: 10.1038/s41467-021-22954-y

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