Expression of CD39 on Activated T Cells Impairs their Survival in Older Individuals
Fengqin Fang,
Mingcan Yu,
Mary M. Cavanagh,
Jessica Hutter Saunders,
Qian Qi,
Zhongde Ye,
Sabine Le Saux,
William Sultan,
Emerson Turgano,
Cornelia L. Dekker,
Lu Tian,
Cornelia M. Weyand,
Jörg J. Goronzy
Affiliations
Fengqin Fang
Departments of Medicine, Pediatrics, and Health Research and Policy, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Palo Alto Veterans Administration Health Care System, Palo Alto, CA 94304, USA
Mingcan Yu
Departments of Medicine, Pediatrics, and Health Research and Policy, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Palo Alto Veterans Administration Health Care System, Palo Alto, CA 94304, USA
Mary M. Cavanagh
Departments of Medicine, Pediatrics, and Health Research and Policy, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Palo Alto Veterans Administration Health Care System, Palo Alto, CA 94304, USA
Jessica Hutter Saunders
Departments of Medicine, Pediatrics, and Health Research and Policy, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Palo Alto Veterans Administration Health Care System, Palo Alto, CA 94304, USA
Qian Qi
Departments of Medicine, Pediatrics, and Health Research and Policy, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Palo Alto Veterans Administration Health Care System, Palo Alto, CA 94304, USA
Zhongde Ye
Departments of Medicine, Pediatrics, and Health Research and Policy, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Palo Alto Veterans Administration Health Care System, Palo Alto, CA 94304, USA
Sabine Le Saux
Departments of Medicine, Pediatrics, and Health Research and Policy, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Palo Alto Veterans Administration Health Care System, Palo Alto, CA 94304, USA
William Sultan
Departments of Medicine, Pediatrics, and Health Research and Policy, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Palo Alto Veterans Administration Health Care System, Palo Alto, CA 94304, USA
Emerson Turgano
Departments of Medicine, Pediatrics, and Health Research and Policy, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Palo Alto Veterans Administration Health Care System, Palo Alto, CA 94304, USA
Cornelia L. Dekker
Departments of Medicine, Pediatrics, and Health Research and Policy, Stanford University School of Medicine, Stanford, CA 94305, USA
Lu Tian
Departments of Medicine, Pediatrics, and Health Research and Policy, Stanford University School of Medicine, Stanford, CA 94305, USA
Cornelia M. Weyand
Departments of Medicine, Pediatrics, and Health Research and Policy, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Palo Alto Veterans Administration Health Care System, Palo Alto, CA 94304, USA
Jörg J. Goronzy
Departments of Medicine, Pediatrics, and Health Research and Policy, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Palo Alto Veterans Administration Health Care System, Palo Alto, CA 94304, USA; Corresponding author
Summary: 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. : 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.
