Exogenous amino acids are essential for interleukin-7 induced CD8 T cell growth. [corrected]

PLoS One. 2012;7(4):e33998. doi: 10.1371/journal.pone.0033998. Epub 2012 Apr 17.

Abstract

IL-7 signalling is important in regulating both survival and cellular size (growth) of T cells. While glucose metabolism has previously been implicated in the mechanism of IL-7 induced survival and growth, the role of amino acids has not before been reported. Here, we show IL-7 dependent T cell survival does not require either exogenous glucose or amino acids. In contrast, maintenance of cell size and IL-7 induced growth were specifically dependent on amino acids. Furthermore, cellular amino acid uptake was implicated in the mechanism of IL-7 induced growth. Analysis of IL-7 regulated gene expression revealed that neutral and cationic amino acid transporters were specific transcriptional targets of IL-7 signalling. In contrast, none of the four glucose transporters expressed in T cells were modulated. Taken together, these data reveal for the first time the central importance of amino acid homeostasis for IL-7 regulated T cell growth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Transport Systems / genetics
  • Amino Acids / pharmacology*
  • Animals
  • CD8-Positive T-Lymphocytes / drug effects*
  • CD8-Positive T-Lymphocytes / metabolism*
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Fusion Regulatory Protein-1 / metabolism
  • Gene Expression / drug effects
  • Glucose / pharmacology
  • Glucose Transport Proteins, Facilitative / genetics
  • Interleukin-7 / pharmacology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Phosphoinositide-3 Kinase Inhibitors
  • TOR Serine-Threonine Kinases / antagonists & inhibitors

Substances

  • Amino Acid Transport Systems
  • Amino Acids
  • Fusion Regulatory Protein-1
  • Glucose Transport Proteins, Facilitative
  • Interleukin-7
  • Phosphoinositide-3 Kinase Inhibitors
  • TOR Serine-Threonine Kinases
  • Glucose