The Proteomic Landscape of Human Ex Vivo Regulatory and Conventional T Cells Reveals Specific Metabolic Requirements

Immunity. 2016 Feb 16;44(2):406-21. doi: 10.1016/j.immuni.2016.01.028.

Abstract

Human CD4(+)CD25(hi)Foxp3(+)CD127(-) Treg and CD4(+)CD25(-)Foxp3(-) Tconv cell functions are governed by their metabolic requirements. Here we report a comprehensive comparative analysis between ex vivo human Treg and Tconv cells that comprises analyses of the proteomic networks in subcellular compartments. We identified a dominant proteomic signature at the metabolic level that primarily impacted the highly-tuned balance between glucose and fatty-acid oxidation in the two cell types. Ex vivo Treg cells were highly glycolytic while Tconv cells used predominantly fatty-acid oxidation (FAO). When cultured in vitro, Treg cells engaged both glycolysis and FAO to proliferate, while Tconv cell proliferation mainly relied on glucose metabolism. Our unbiased proteomic analysis provides a molecular picture of the impact of metabolism on ex vivo human Treg versus Tconv cell functions that might be relevant for therapeutic manipulations of these cells.

Keywords: Conventional T cells; Immune Tolerance; Metabolism; Proteomic Analysis; Regulatory T cells.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4 Antigens / metabolism
  • Cell Proliferation
  • Cells, Cultured
  • Fatty Acids / metabolism*
  • Forkhead Transcription Factors / metabolism
  • Glucose / metabolism*
  • Glycolysis*
  • Humans
  • Interleukin-2 Receptor alpha Subunit / metabolism
  • Oxidation-Reduction
  • Proteomics
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocytes, Regulatory / immunology*
  • Transcriptome

Substances

  • CD4 Antigens
  • FOXP3 protein, human
  • Fatty Acids
  • Forkhead Transcription Factors
  • Interleukin-2 Receptor alpha Subunit
  • Glucose