The Proteomic Landscape of Resting and Activated CD4+ T Cells Reveal Insights into Cell Differentiation and Function

Int J Mol Sci. 2020 Dec 29;22(1):275. doi: 10.3390/ijms22010275.

Abstract

CD4+ T cells (T helper cells) are cytokine-producing adaptive immune cells that activate or regulate the responses of various immune cells. The activation and functional status of CD4+ T cells is important for adequate responses to pathogen infections but has also been associated with auto-immune disorders and survival in several cancers. In the current study, we carried out a label-free high-resolution FTMS-based proteomic profiling of resting and T cell receptor-activated (72 h) primary human CD4+ T cells from peripheral blood of healthy donors as well as SUP-T1 cells. We identified 5237 proteins, of which significant alterations in the levels of 1119 proteins were observed between resting and activated CD4+ T cells. In addition to identifying several known T-cell activation-related processes altered expression of several stimulatory/inhibitory immune checkpoint markers between resting and activated CD4+ T cells were observed. Network analysis further revealed several known and novel regulatory hubs of CD4+ T cell activation, including IFNG, IRF1, FOXP3, AURKA, and RIOK2. Comparison of primary CD4+ T cell proteomic profiles with human lymphoblastic cell lines revealed a substantial overlap, while comparison with mouse CD+ T cell data suggested interspecies proteomic differences. The current dataset will serve as a valuable resource to the scientific community to compare and analyze the CD4+ proteome.

Keywords: CD4+ T helper cells; T-lymphocytes; adaptive immunity; label-free quantitation; mass spectrometry; proteomics; systems biology.

MeSH terms

  • Adaptive Immunity
  • Animals
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism*
  • Cell Differentiation* / genetics
  • Cell Differentiation* / immunology
  • Cell Line
  • Humans
  • Immune Checkpoint Proteins / metabolism
  • Lymphocyte Activation* / genetics
  • Lymphocyte Activation* / immunology
  • Mass Spectrometry
  • Mice
  • Proteome*
  • Proteomics* / methods
  • Signal Transduction

Substances

  • Immune Checkpoint Proteins
  • Proteome