AMPK α1: A glucose sensor that controls CD 8 T‐cell memory

J Rolf, M Zarrouk, DK Finlay, M Foretz… - European journal of …, 2013 - Wiley Online Library
J Rolf, M Zarrouk, DK Finlay, M Foretz, B Viollet, DA Cantrell
European journal of immunology, 2013Wiley Online Library
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 CD 8 T lymphocytes to the metabolically quiescent catabolic memory T cells during
the contraction phase of the immune response. We show that AMPK α1 activates rapidly in …
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 AMPKα1 activates rapidly in response to the metabolic stress caused by glucose deprivation of CD8 cytotoxic T lymphocytes (CTLs). Moreover, AMPKα1 restrains mammalian target of rapamycin complex 1 activity under conditions of glucose stress. AMPKα1 activity is dispensable for proliferation and differentiation of CTLs. However, AMPKα1 is required for in vivo survival of CTLs following withdrawal of immune stimulation. AMPKα1null 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 AMPKα1 monitors energy stress in CTLs and controls CD8 T‐cell memory.
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