Asymmetric cell division shapes naive and virtual memory T-cell immunity during ageing.
Mariana BorsaNiculò BarandunFabienne GräbnitzIsabel BarnstorfNicolas S BaumannKatharina PallmerSamira BaumannDominique StarkMiroslav BalazNathalie OetikerFranziska WagenChristian WolfrumAnna Katharina SimonNicole JollerYves BarralRoman SpörriAnnette OxeniusPublished in: Nature communications (2021)
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.
Keyphrases
- immune response
- induced apoptosis
- single cell
- working memory
- cell cycle arrest
- signaling pathway
- cell therapy
- hiv infected
- high fat diet induced
- stem cells
- cell proliferation
- machine learning
- electronic health record
- endoplasmic reticulum stress
- oxidative stress
- cell death
- mesenchymal stem cells
- adipose tissue
- human health
- climate change
- pi k akt
- bone marrow
- big data
- artificial intelligence
- solid state
- cerebral ischemia
- wild type