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

• CD39 identifies human effector CD4 T cells that are prone to apoptosis
• CD39 is more readily induced in CD4 T cell responses of older individuals
• The ATPase activity of CD39 regulates effector cell differentiation and apoptosis
• CD39 expression inversely correlates with T memory cell generation after vaccination

SummaryIn 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.

Graphical AbstractFigure optionsDownload as PowerPoint slide