Mitochondrial Respiratory Capacity is a Critical Regulator of CD8+ T Cell Memory Development

Overview

Journal Immunity

Publisher Cell Press

Specialty Allergy & Immunology

Date 2011 Dec 31

PMID 22206904

Citations 851

Authors

Gerritje J W van der Windt

Bart Everts

Chih-Hao Chang

Jonathan D Curtis

Tori C Freitas

Eyal Amiel

Edward J Pearce

Erika L Pearce

Affiliations

Soon will be listed here.

Abstract

CD8(+) T cells undergo major metabolic changes upon activation, but how metabolism influences the establishment of long-lived memory T cells after infection remains a key question. We have shown here that CD8(+) memory T cells, but not CD8(+) T effector (Teff) cells, possessed substantial mitochondrial spare respiratory capacity (SRC). SRC is the extra capacity available in cells to produce energy in response to increased stress or work and as such is associated with cellular survival. We found that interleukin-15 (IL-15), a cytokine critical for CD8(+) memory T cells, regulated SRC and oxidative metabolism by promoting mitochondrial biogenesis and expression of carnitine palmitoyl transferase (CPT1a), a metabolic enzyme that controls the rate-limiting step to mitochondrial fatty acid oxidation (FAO). These results show how cytokines control the bioenergetic stability of memory T cells after infection by regulating mitochondrial metabolism.

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