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

• Published in: Cell reports (Cambridge) Vol. 14; no. 5; pp. 1218 - 1231
• Main Authors: Fang, Fengqin, Yu, Mingcan, Cavanagh, Mary M., Hutter Saunders, Jessica, Qi, Qian, Ye, Zhongde, Le Saux, Sabine, Sultan, William, Turgano, Emerson, Dekker, Cornelia L., Tian, Lu, Weyand, Cornelia M., Goronzy, Jörg J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 09.02.2016; Elsevier
• Subjects: 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
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2016.01.002

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. [Display omitted] •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 Fang et al. report that the ATPase activity of CD39 regulates differentiation and apoptosis of effector T cells. They propose that increased CD39 expression in T cells with age promotes T cell apoptosis in older individuals and contributes to age-dependent impairment in responses to vaccination.