PMID: 32231301 DOI: 10.1038/s41590-020-0643-3
Pereira, De Maeyer, Covre, Nehar-Belaid et al. Nature Immunology. 2020
Sestrins induce natural killer function in senescent-like CD8+ T cells
We used single-cell RNA sequencing (scRNA-seq) to investigate the transcriptomes of ~62,000 CD8+ T cells isolated from six healthy older donors (72–88 y). CD8+IL-7R+ and CD8+IL-7R− T cells were sorted from each donor resulting in 12 samples.
https://ega-archive.org/studies/EGAS00001004255
accession number EGAS00001004255
The complete microarray data set is available here: GEO accession number GSE98640
Aging is associated with remodeling of the immune system to enable the maintenance of life-long immunity. In the CD8+ T cell compartment, aging results in the expansion of highly differentiated cells that exhibit characteristics of cellular senescence. Here we found that CD27−CD28−CD8+ T cells lost the signaling activity of the T cell antigen receptor (TCR) and expressed a protein complex containing the agonistic natural killer (NK) receptor NKG2D and the NK adaptor molecule DAP12, which promoted cytotoxicity against cells that expressed NKG2D ligands. Immunoprecipitation and imaging cytometry indicated that the NKG2D– DAP12 complex was associated with sestrin 2. The genetic inhibition of sestrin 2 resulted in decreased expression of NKG2D and DAP12 and restored TCR signaling in senescent-like CD27−CD28−CD8+ T cells. Therefore, during aging, sestrins induce the reprogramming of non-proliferative senescent-like CD27−CD28−CD8+ T cells to acquire a broad-spectrum, innate-like killing activity.