Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 110, Issue 35, Pages 14336-14341Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1221740110
Keywords
metabolism; lymphocytes
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Funding
- National Institutes of Health
- Netherlands Organisation for Scientific Research
- NATIONAL CANCER INSTITUTE [R01CA164062] Funding Source: NIH RePORTER
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A characteristic of memory T (T-M) cells is their ability to mount faster and stronger responses to reinfection than naive T (T-N) cells do in response to an initial infection. However, the mechanisms that allow this rapid recall are not completely understood. We found that CD8 T-M cells have more mitochondrial mass than CD8 T-N cells and, that upon activation, the resulting secondary effector T (T-E) cells proliferate more quickly, produce more cytokines, and maintain greater ATP levels than primary effector T cells. We also found that after activation, T-M cells increase oxidative phosphorylation and aerobic glycolysis and sustain this increase to a greater extent than T-N cells, suggesting that greater mitochondrial mass in T-M 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 T-N and T-M cells. We also found that fatty acid oxidation is needed for T-M 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 receptor stimulation in T-M cells. Our results demonstrate that greater mitochondrial mass endows T-M cells with a bioenergetic advantage that underlies their ability to rapidly recall in response to reinfection.
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