Continuous T cell receptor signals maintain a functional regulatory T cell pool

Immunity. 2014 Nov 20;41(5):722-36. doi: 10.1016/j.immuni.2014.10.012. Epub 2014 Nov 6.

Abstract

Regulatory T (Treg) cells maintain immune homeostasis and prevent inflammatory and autoimmune responses. During development, thymocytes bearing a moderately self-reactive T cell receptor (TCR) can be selected to become Treg cells. Several observations suggest that also in the periphery mature Treg cells continuously receive self-reactive TCR signals. However, the importance of this inherent autoreactivity for Treg cell biology remains poorly defined. To address this open question, we genetically ablated the TCR of mature Treg cells in vivo. These experiments revealed that TCR-induced Treg lineage-defining Foxp3 expression and gene hypomethylation were uncoupled from TCR input in mature Treg cells. However, Treg cell homeostasis, cell-type-specific gene expression and suppressive function critically depend on continuous triggering of their TCR.

MeSH terms

  • Animals
  • Autoimmunity / immunology*
  • Cell Differentiation / immunology
  • Cell Lineage / immunology
  • DNA Methylation / immunology
  • DNA-Binding Proteins / genetics
  • Forkhead Transcription Factors / biosynthesis*
  • Forkhead Transcription Factors / genetics
  • Inflammation / immunology
  • Interferon Regulatory Factors / biosynthesis
  • Mechanistic Target of Rapamycin Complex 1
  • Mechanistic Target of Rapamycin Complex 2
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Multiprotein Complexes / metabolism
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, Antigen, T-Cell, alpha-beta / immunology*
  • Signal Transduction / immunology
  • T-Lymphocytes, Regulatory / immunology*
  • TOR Serine-Threonine Kinases / metabolism
  • Thymocytes / cytology

Substances

  • DNA-Binding Proteins
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Interferon Regulatory Factors
  • Multiprotein Complexes
  • Rag2 protein, mouse
  • Receptors, Antigen, T-Cell, alpha-beta
  • interferon regulatory factor-4
  • TOR Serine-Threonine Kinases
  • Mechanistic Target of Rapamycin Complex 1
  • Mechanistic Target of Rapamycin Complex 2

Associated data

  • GEO/GSE62532