AMPKα1: a glucose sensor that controls CD8 T-cell memory

Julia Rolf, Marouan Zarrouk, David K. Finlay, Marc Foretz, Benoit Viollet, Doreen A. Cantrell

    Research output: Contribution to journalArticle

    106 Citations (Scopus)

    Abstract

    The adenosine monophosphate-activated protein kinase (AMPK) is activated by antigen receptor signals and energy stress in T cells. In many cell types, AMPK can maintain energy homeostasis and can enforce quiescence to limit energy demands. We consequently evaluated the importance of AMPK for controlling the transition of metabolically active effector CD8 T lymphocytes to the metabolically quiescent catabolic memory T cells during the contraction phase of the immune response. We show that AMPK1 activates rapidly in response to the metabolic stress caused by glucose deprivation of CD8 cytotoxic T lymphocytes (CTLs). Moreover, AMPK1 restrains mammalian target of rapamycin complex 1 activity under conditions of glucose stress. AMPK1 activity is dispensable for proliferation and differentiation of CTLs. However, AMPK1 is required for in vivo survival of CTLs following withdrawal of immune stimulation. AMPK1null T cells also show a striking defect in their ability to generate memory CD8 T-cell responses during Listeria monocytogenes infection. These results show that AMPK1 monitors energy stress in CTLs and controls CD8 T-cell memory.

    Original languageEnglish
    Pages (from-to)889-896
    Number of pages8
    JournalEuropean Journal of Immunology
    Volume43
    Issue number4
    DOIs
    Publication statusPublished - Apr 2013

    Keywords

    • ENERGY SENSOR
    • LYMPHOCYTES
    • Listeria monocytogenes
    • METFORMIN
    • REGULATOR
    • Energy stress
    • EFFECTOR
    • AMPK
    • DIFFERENTIATION
    • Memory
    • ACTIVATED PROTEIN-KINASE
    • GROWTH
    • METABOLISM
    • Cytotoxic T lymphocyte
    • Metabolism

    Cite this

    Rolf, Julia ; Zarrouk, Marouan ; Finlay, David K. ; Foretz, Marc ; Viollet, Benoit ; Cantrell, Doreen A. / AMPKα1 : a glucose sensor that controls CD8 T-cell memory. In: European Journal of Immunology. 2013 ; Vol. 43, No. 4. pp. 889-896.
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    abstract = "The adenosine monophosphate-activated protein kinase (AMPK) is activated by antigen receptor signals and energy stress in T cells. In many cell types, AMPK can maintain energy homeostasis and can enforce quiescence to limit energy demands. We consequently evaluated the importance of AMPK for controlling the transition of metabolically active effector CD8 T lymphocytes to the metabolically quiescent catabolic memory T cells during the contraction phase of the immune response. We show that AMPK1 activates rapidly in response to the metabolic stress caused by glucose deprivation of CD8 cytotoxic T lymphocytes (CTLs). Moreover, AMPK1 restrains mammalian target of rapamycin complex 1 activity under conditions of glucose stress. AMPK1 activity is dispensable for proliferation and differentiation of CTLs. However, AMPK1 is required for in vivo survival of CTLs following withdrawal of immune stimulation. AMPK1null T cells also show a striking defect in their ability to generate memory CD8 T-cell responses during Listeria monocytogenes infection. These results show that AMPK1 monitors energy stress in CTLs and controls CD8 T-cell memory.",
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    author = "Julia Rolf and Marouan Zarrouk and Finlay, {David K.} and Marc Foretz and Benoit Viollet and Cantrell, {Doreen A.}",
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    Rolf, J, Zarrouk, M, Finlay, DK, Foretz, M, Viollet, B & Cantrell, DA 2013, 'AMPKα1: a glucose sensor that controls CD8 T-cell memory', European Journal of Immunology, vol. 43, no. 4, pp. 889-896. https://doi.org/10.1002/eji.201243008

    AMPKα1 : a glucose sensor that controls CD8 T-cell memory. / Rolf, Julia; Zarrouk, Marouan; Finlay, David K.; Foretz, Marc; Viollet, Benoit; Cantrell, Doreen A.

    In: European Journal of Immunology, Vol. 43, No. 4, 04.2013, p. 889-896.

    Research output: Contribution to journalArticle

    TY - JOUR

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    T2 - a glucose sensor that controls CD8 T-cell memory

    AU - Rolf, Julia

    AU - Zarrouk, Marouan

    AU - Finlay, David K.

    AU - Foretz, Marc

    AU - Viollet, Benoit

    AU - Cantrell, Doreen A.

    PY - 2013/4

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    N2 - The adenosine monophosphate-activated protein kinase (AMPK) is activated by antigen receptor signals and energy stress in T cells. In many cell types, AMPK can maintain energy homeostasis and can enforce quiescence to limit energy demands. We consequently evaluated the importance of AMPK for controlling the transition of metabolically active effector CD8 T lymphocytes to the metabolically quiescent catabolic memory T cells during the contraction phase of the immune response. We show that AMPK1 activates rapidly in response to the metabolic stress caused by glucose deprivation of CD8 cytotoxic T lymphocytes (CTLs). Moreover, AMPK1 restrains mammalian target of rapamycin complex 1 activity under conditions of glucose stress. AMPK1 activity is dispensable for proliferation and differentiation of CTLs. However, AMPK1 is required for in vivo survival of CTLs following withdrawal of immune stimulation. AMPK1null T cells also show a striking defect in their ability to generate memory CD8 T-cell responses during Listeria monocytogenes infection. These results show that AMPK1 monitors energy stress in CTLs and controls CD8 T-cell memory.

    AB - The adenosine monophosphate-activated protein kinase (AMPK) is activated by antigen receptor signals and energy stress in T cells. In many cell types, AMPK can maintain energy homeostasis and can enforce quiescence to limit energy demands. We consequently evaluated the importance of AMPK for controlling the transition of metabolically active effector CD8 T lymphocytes to the metabolically quiescent catabolic memory T cells during the contraction phase of the immune response. We show that AMPK1 activates rapidly in response to the metabolic stress caused by glucose deprivation of CD8 cytotoxic T lymphocytes (CTLs). Moreover, AMPK1 restrains mammalian target of rapamycin complex 1 activity under conditions of glucose stress. AMPK1 activity is dispensable for proliferation and differentiation of CTLs. However, AMPK1 is required for in vivo survival of CTLs following withdrawal of immune stimulation. AMPK1null T cells also show a striking defect in their ability to generate memory CD8 T-cell responses during Listeria monocytogenes infection. These results show that AMPK1 monitors energy stress in CTLs and controls CD8 T-cell memory.

    KW - ENERGY SENSOR

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    KW - EFFECTOR

    KW - AMPK

    KW - DIFFERENTIATION

    KW - Memory

    KW - ACTIVATED PROTEIN-KINASE

    KW - GROWTH

    KW - METABOLISM

    KW - Cytotoxic T lymphocyte

    KW - Metabolism

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    M3 - Article

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    JO - European Journal of Immunology

    JF - European Journal of Immunology

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    ER -