Mitochondrial Respiratory Capacity Is A Critical Regulator Of CD8+ T Cell Memory Development

By G. V. D. van der Windt, B. Everts, Chih-Hao Chang, Jonathan D. Curtis, T. Freitas, Eyal Amiel, Edward J. Pearce, Erika L. Pearce. Immunity, 2011

1,466 citations recorded by the source corpus.

Summary CD8+ T cells undergo major metabolic changes upon activation, but how metabolism influences the establishment of long-lived memory T (TM) cells after infection remains a key question. We have shown here that CD8+ TM cells, but not effector CD8+ (TE) 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+ TM 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 TM cells after infection by regulating mitochondrial metabolism.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/47d757dfbbdc0809cee02e2fa1ccb09bd28d62c1

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

1. Erika L. Pearce
2. S. Kaech
3. Michael D. Buck
4. F. Sallusto
5. A. Lanzavecchia
6. N. Restifo
7. E. Wherry
8. R. Sowell

Citations in the corpus

• The energy sensor AMPK regulates T cell metabolic adaptation and effector responses in vivo. (2015, background): “Mitochondrial spare respiratory capacity (SRC) is defined as the increase in OCR following uncoupling with FCCP (van der Windt et al., 2012).”
• Metabolic Regulation of Immune Responses (2014, background): “demonstrated that IL-15 stimulates mitochondrial biogenesis and increases mitochondrial respiratory capacity in CD8+ memory T cells, thereby enhancing ability of CD8+ memory T cells to survive in metabolically stressful conditions (104).”
• Metabolic Pathways In Immune Cell Activation And Quiescence (2013, background): “In contrast to effector T cells, which use glycolysis and have reduced mitochondrial mass, memory T cells maintain greater mitochondrial mass, a fact which supports their oxidative metabolism (van der Windt et al., 2012).”
• Distinct Signaling of Coreceptors Regulates Specific Metabolism Pathways and Impacts Memory Development in CAR T Cells. (2016, background): “Increasing evidence has demonstrated a role for carnitine palmitoyl transferase (CPT1A) in regulating oxidative metabolism in CD8+ memory T cells (van der Windt et al., 2012).”
• The Glucose Transporter Glut1 is Selectively Essential for CD4 T Cell Activation and Effector Function (2014, positive): “Likewise, effector CD8 T cells are glycolytic, whereas memory CD8 T cells utilize lipid oxidation (Gubser et al., 2013; Pearce et al., 2009; van der Windt et al., 2012).”