CD8 memory T cells have a bioenergetic advantage that underlies their rapid recall ability
A characteristic of memory T (T M) cells is their ability to mount faster and stronger responses to reinfection than naïve 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 m...
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Published in | Proceedings of the National Academy of Sciences - PNAS Vol. 110; no. 35; pp. 14336 - 14341 |
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Main Authors | , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
National Academy of Sciences
27.08.2013
National Acad Sciences |
Subjects | |
Online Access | Get full text |
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Summary: | A characteristic of memory T (T M) cells is their ability to mount faster and stronger responses to reinfection than naïve 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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Bibliography: | http://dx.doi.org/10.1073/pnas.1221740110 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Author contributions: G.J.W.v.d.W., D.O., B.E., S.C.-C.H., C.-H.C., R.G.J., E.J.P., and E.L.P. designed research; G.J.W.v.d.W., D.O., S.C.-C.H., M.D.B., J.D.C., C.-H.C., A.M.S., T.A., and B.F. performed research; G.J.W.v.d.W., D.O., J.D.C., B.F., and E.L.P. analyzed data; and G.J.W.v.d.W. and E.L.P. wrote the paper. Edited by Rafi Ahmed, Emory University, Atlanta, GA, and approved July 9, 2013 (received for review December 12, 2012) |
ISSN: | 0027-8424 1091-6490 |
DOI: | 10.1073/pnas.1221740110 |