Altered basal lipid metabolism underlies the functional impairment of naive CD8+ T cells in elderly humans

Nicoli et al. (BioRxiv) DOI: 10.1101/2020.09.24.311704

 

Keywords

  • Fatty acid metabolism

  • ageing

  • naïve CD8 T cells

 

Main Findings

​Naïve CD8 T cells from elderly individuals show reduced proliferation upon T cell receptor (TCR) ligation, which correlates with an increase in cells that show pro-apoptotic activate caspase-3 and a high basal activation state defined by increased percentage of T-bet positive cells. Metabolic analysis of these aged naïve CD8 T cells demonstrate that the higher basal activation state corresponds to an increase in fatty acid uptake and neutral lipid storage. Reducing stored neutral lipids by treating these cells with the drug Rosiglitazone restores T cell proliferation in vitro.

Limitations

  • Limited patient information and method description (what positive/negative controls, what sorted cell population was used in each experiment, etc).

  • The group is split in 2 very broad age-ranges. It would be better to not split in separate groups but have the age on one axe and the metabolic parameter on the other.

  • Observed changes in glycolytic enzymes upon TCR ligation are not followed through. Are these changes in response to the altered lipid metabolism in the basal state? 

  • Does Rosiglitazone also restore the other T cell defects reported in their 2016 publication (O. Bricena et al Aging Cell 2016), such as Granzyme B and Perforin expression

  • mRNA levels of HIF1a and RPS6KB1 in quiescent naïve CD8 T cells are not reported, only that they are significantly differently upregulated upon TCR ligation.

Significance/Novelty

The study identifies an age-related link between altered basal lipid metabolism in naive CD8 T cells and their impaired responsiveness to stimulation, in human naïve CD8 T cells from elderly individuals. Importantly, they show that reversal of the bioenergetic anomalies with lipid-altering drug rosiglitazone, improved the functional capabilities of these human aged naive CD8+ T cells.​

Credit 

Reviewed by Ewoud Compeer as part of the cross-institutional journal club of the Immunology Institute of the Icahn School of Medicine, Mount Sinai and the Kennedy Institute of Rheumatology, University of Oxford. Follow him on Twitter.