Expression of CD39 on Activated T Cells Impairs Their Survival in Older Individuals

Cell Rep. 2016 Feb 9;14(5):1218-1231. doi: 10.1016/j.celrep.2016.01.002. Epub 2016 Jan 28.

Abstract

In an immune response, CD4(+) T cells expand into effector T cells and then contract to survive as long-lived memory cells. To identify age-associated defects in memory cell formation, we profiled activated CD4(+) T cells and found an increased induction of the ATPase CD39 with age. CD39(+) CD4(+) T cells resembled effector T cells with signs of metabolic stress and high susceptibility to undergo apoptosis. Pharmacological inhibition of ATPase activity dampened effector cell differentiation and improved survival, suggesting that CD39 activity influences T cell fate. Individuals carrying a low-expressing CD39 variant responded better to vaccination with an increase in vaccine-specific memory T cells. Increased inducibility of CD39 after activation may contribute to the impaired vaccine response with age.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenosine Triphosphatases / metabolism
  • Adult
  • Aged
  • Aged, 80 and over
  • Aging / immunology*
  • Antigens, CD / metabolism*
  • Apoptosis
  • Apyrase / metabolism*
  • CD4-Positive T-Lymphocytes / cytology*
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Proliferation
  • Cell Survival
  • Clone Cells
  • Humans
  • Lymphocyte Activation / immunology*
  • Middle Aged
  • Stress, Physiological
  • Young Adult

Substances

  • Antigens, CD
  • Adenosine Triphosphatases
  • ectoATPase
  • Apyrase
  • CD39 antigen