Sestrins induce natural killer function in senescent-like CD8
Document Type
Article
Publication Date
6-1-2020
Keywords
JGM, JAXCC
JAX Source
Nat Immunol 2020 Jun; 21(6):684-694
Volume
21
Issue
6
First Page
684
Last Page
694
ISSN
1529-2916
PMID
32231301
DOI
https://doi.org/10.1038/s41590-020-0643-3
Abstract
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.
Recommended Citation
Pereira B,
De Maeyer R,
Covre L,
Nehar-Belaid D,
Lanna A,
Ward S,
Marches R,
Chambers E,
Gomes D,
Riddell N,
Maini M,
Teixeira V,
Janes S,
Gilroy D,
Larbi A,
Mabbott N,
Ucar D,
Kuchel G,
Henson S,
Strid J,
Lee J,
Banchereau J,
Akbar A.
Sestrins induce natural killer function in senescent-like CD8 Nat Immunol 2020 Jun; 21(6):684-694