Human CD8+ EMRA T cells display a senescence-associated secretory phenotype regulated by p38 MAPK

Aging Cell. 2018 Feb;17(1):e12675. doi: 10.1111/acel.12675. Epub 2017 Oct 12.

Abstract

Cellular senescence is accompanied by a senescence-associated secretory phenotype (SASP). We show here that primary human senescent CD8+ T cells also display a SASP comprising chemokines, cytokines and extracellular matrix remodelling proteases that are unique to this subset and contribute to age-associated inflammation. We found the CD8+ CD45RA+ CD27- EMRA subset to be the most heterogeneous, with a population aligning with the naïve T cells and another with a closer association to the effector memory subset. However, despite the differing processes that give rise to these senescent CD8+ T cells once generated, they both adopt a unique secretory profile with no commonality to any other subset, aligning more closely with senescence than quiescence. Furthermore, we also show that the SASP observed in senescent CD8+ T cells is governed by p38 MAPK signalling.

Keywords: SASP; T cell; aging; cytokine; inflammation; microarray.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CD8-Positive T-Lymphocytes / cytology*
  • Cellular Senescence / genetics*
  • Cytokines / genetics*
  • Cytokines / metabolism
  • DNA Damage / genetics
  • Healthy Volunteers
  • Humans
  • MAP Kinase Signaling System / genetics
  • Middle Aged
  • Phenotype
  • p38 Mitogen-Activated Protein Kinases / genetics*
  • p38 Mitogen-Activated Protein Kinases / immunology

Substances

  • Cytokines
  • p38 Mitogen-Activated Protein Kinases