Asymmetric cell division shapes naive and virtual memory T-cell immunity during ageing
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Date
2021-05-11
Publication Type
Journal Article
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yes
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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.
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published
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Journal / series
Volume
12 (1)
Pages / Article No.
2715
Publisher
Nature
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Edition / version
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Date collected
Date created
Subject
Adaptive immunity; Immunological Memory; Lymphocyte differentiation; T cells
Organisational unit
03532 - Barral, Yves / Barral, Yves
03625 - Oxenius, Annette / Oxenius, Annette
03819 - Wolfrum, Christian (ehemalig) / Wolfrum, Christian (former)
Notes
Funding
166078 - Antibody evolution during chronic viral infections: a functional and systems immunological approach (SNF)