Sestrins induce natural killer function in senescent-like CD8+ T cells

Branca I. Pereira, Roel P. H. De Maeyer , Luciana P. Covre, Djamel Nehar-Belaid, Alessio Lanna, Sophie Ward , Radu Marches , Emma S Chambers, Daniel C. O. Gomes , Natalie E. Riddell , Mala K. Maini, Vitor H. Teixeira, Samuel M. Janes , Derek W Gilroy, Anis Larbi, Neil Mabbott, Duyga Ucar, George A. Kuchel, Sian M. Henson, Jessica StridJun H. Lee , Jacques Banchereau , Arne N Akbar

Research output: Contribution to journalArticlepeer-review

Abstract

Ageing is associated with re-modelling of the immune system to enable the maintenance of life-long immunity. In the CD8+ T cell compartment, ageing results in the expansion of highly differentiated cells that exhibit characteristics of cellular senescence. Here we found that CD27-CD28-CD8+ T lost the signalling activity of the T cell antigen receptor (TCR) and expressed a protein complex containing the agonistic 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 (Sesn2). The genetic inhibition of Sesn2 resulted in decreased expression of NKG2D and DAP12 and restored TCR signaling in senescent-like CD27-CD28-CD8+ T cells. Therefore, during ageing, sestrins induces the reprogramming of non-proliferative senescent-like CD27-CD28-CD8+ T cells to acquire a broad-spectrum,
innate-like killing activity.
Original languageEnglish
JournalNature Immunology
DOIs
Publication statusPublished - 30 Mar 2020

Keywords

  • CD8-positive T cells
  • Cellular immunity
  • Immunosurveillance

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