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

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 tra...

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Bibliographic Details
Published in:Nature communications 2021-05, Vol.12 (1), p.2715-2715, Article 2715
Main Authors: Borsa, Mariana, Barandun, Niculò, Gräbnitz, Fabienne, Barnstorf, Isabel, Baumann, Nicolas S., Pallmer, Katharina, Baumann, Samira, Stark, Dominique, Balaz, Miroslav, Oetiker, Nathalie, Wagen, Franziska, Wolfrum, Christian, Simon, Anna Katharina, Joller, Nicole, Barral, Yves, Spörri, Roman, Oxenius, Annette
Format: Article
Language:English
Subjects:
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Aging
Asymmetry
CD8 antigen
Cell division
Cell proliferation
Heterogeneity
Humanities and Social Sciences
Immune system
Immunity
Immunological memory
Lymphocytes
Lymphocytes T
Memory cells
multidisciplinary
Phenotypes
Science
Science (multidisciplinary)
TOR protein
Virtual memory systems
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Summary: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 (T VM 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. Asymmetrical cell division helps to maintain cellular heterogeneity in the T cell compartment. Here the authors examine the differential immune responses built by naive and virtual memory T cells from young and aged individuals, and explore the effect of mTOR inhibition on asymmetrical cell division and memory formation.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-021-22954-y