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

doi:10.1016/j.celrep.2016.01.002

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

Immunology

Research output: Contribution to journal › Article › peer-review

56 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1218-1231
Number of pages	14
Journal	Cell reports
Volume	14
Issue number	5
DOIs	https://doi.org/10.1016/j.celrep.2016.01.002
State	Published - Feb 9 2016

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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10.1016/j.celrep.2016.01.002

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title = "Expression of CD39 on Activated T Cells Impairs their Survival in Older Individuals",

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.",

author = "Fengqin Fang and Mingcan Yu and Cavanagh, {Mary M.} and {Hutter Saunders}, Jessica and Qian Qi and Zhongde Ye and {Le Saux}, Sabine and William Sultan and Emerson Turgano and Dekker, {Cornelia L.} and Lu Tian and Weyand, {Cornelia M.} and Goronzy, {J{\"o}rg J.}",

note = "Funding Information: This work was supported by NIH grants U19 AI090019, R01 AG015043, U19 AI057266, U01 AI089859-IOF, I01 BX001669, and R01 AI108891 (to J.J.G.) and R01 AR042547, R01 EY011916, R01 AI044142, R01 AI108906, R01 HL117913, and P01 HL058000 (to C.M.W.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Publisher Copyright: {\textcopyright} 2016 The Authors.",

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doi = "10.1016/j.celrep.2016.01.002",

language = "English (US)",

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AU - Fang, Fengqin

AU - Yu, Mingcan

AU - Cavanagh, Mary M.

AU - Hutter Saunders, Jessica

AU - Qi, Qian

AU - Ye, Zhongde

AU - Le Saux, Sabine

AU - Sultan, William

AU - Turgano, Emerson

AU - Dekker, Cornelia L.

AU - Tian, Lu

AU - Weyand, Cornelia M.

AU - Goronzy, Jörg J.

N1 - Funding Information: This work was supported by NIH grants U19 AI090019, R01 AG015043, U19 AI057266, U01 AI089859-IOF, I01 BX001669, and R01 AI108891 (to J.J.G.) and R01 AR042547, R01 EY011916, R01 AI044142, R01 AI108906, R01 HL117913, and P01 HL058000 (to C.M.W.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Publisher Copyright: © 2016 The Authors.

PY - 2016/2/9

Y1 - 2016/2/9

N2 - 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.

AB - 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.

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

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