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Metabolic reprogramming towards aerobic glycolysis correlates with greater proliferative ability and resistance to metabolic inhibition in CD8 versus CD4 T cells.

Publication ,  Journal Article
Cao, Y; Rathmell, JC; Macintyre, AN
Published in: PLoS One
2014

T lymphocytes (T cells) undergo metabolic reprogramming after activation to provide energy and biosynthetic materials for growth, proliferation and differentiation. Distinct T cell subsets, however, adopt metabolic programs specific to support their needs. As CD4 T cells coordinate adaptive immune responses while CD8 T cells become cytotoxic effectors, we compared activation-induced proliferation and metabolic reprogramming of these subsets. Resting CD4 and CD8 T cells were metabolically similar and used a predominantly oxidative metabolism. Following activation CD8 T cells proliferated more rapidly. Stimulation led both CD4 and CD8 T cells to sharply increase glucose metabolism and adopt aerobic glycolysis as a primary metabolic program. Activated CD4 T cells, however, remained more oxidative and had greater maximal respiratory capacity than activated CD8 T cells. CD4 T cells were also associated with greater levels of ROS and increased mitochondrial content, irrespective of the activation context. CD8 cells were better able, however, to oxidize glutamine as an alternative fuel source. The more glycolytic metabolism of activated CD8 T cells correlated with increased capacity for growth and proliferation, along with reduced sensitivity of cell growth to metabolic inhibition. These specific metabolic programs may promote greater growth and proliferation of CD8 T cells and enhance survival in diverse nutrient conditions.

Duke Scholars

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Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2014

Volume

9

Issue

8

Start / End Page

e104104

Location

United States

Related Subject Headings

  • T-Lymphocytes, Cytotoxic
  • Mitochondria
  • Mice
  • Metabolic Networks and Pathways
  • Lymphocyte Activation
  • Glycolysis
  • Glucose
  • General Science & Technology
  • Cell Lineage
  • CD8-Positive T-Lymphocytes
 

Citation

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2014

Volume

9

Issue

8

Start / End Page

e104104

Location

United States

Related Subject Headings

  • T-Lymphocytes, Cytotoxic
  • Mitochondria
  • Mice
  • Metabolic Networks and Pathways
  • Lymphocyte Activation
  • Glycolysis
  • Glucose
  • General Science & Technology
  • Cell Lineage
  • CD8-Positive T-Lymphocytes