Aug 14, 2013

CD8 memory T cells have a bioenergetic advantage that underlies their rapid recall ability

Proceedings of the National Academy of Sciences of the United States of America
Gerritje J W van der WindtErika L Pearce

Abstract

A characteristic of memory T (TM) cells is their ability to mount faster and stronger responses to reinfection than naïve T (TN) cells do in response to an initial infection. However, the mechanisms that allow this rapid recall are not completely understood. We found that CD8 TM cells have more mitochondrial mass than CD8 TN cells and, that upon activation, the resulting secondary effector T (TE) cells proliferate more quickly, produce more cytokines, and maintain greater ATP levels than primary effector T cells. We also found that after activation, TM cells increase oxidative phosphorylation and aerobic glycolysis and sustain this increase to a greater extent than TN cells, suggesting that greater mitochondrial mass in TM cells not only promotes oxidative capacity, but also glycolytic capacity. We show that mitochondrial ATP is essential for the rapid induction of glycolysis in response to activation and the initiation of proliferation of both TN and TM cells. We also found that fatty acid oxidation is needed for TM cells to rapidly respond upon restimulation. Finally, we show that dissociation of the glycolysis enzyme hexokinase from mitochondria impairs proliferation and blocks the rapid induction of glycolysis upon T-cell r...Continue Reading

Mentioned in this Paper

Fatty Acid Oxidation
Energy Metabolism
Suppressor T-Lymphocytes, CD8-Positive
Transcription Initiation
Hexokinase
Sustain
HK1
Mitochondrial Volume
Lymphocyte Activation
Mitochondria

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