TGF-β and Eomes control the homeostasis of CD8+ regulatory T cells

J Exp Med. 2021 Jan 4;218(1):e20200030. doi: 10.1084/jem.20200030.

Abstract

In addition to Foxp3+ CD4+ regulatory T cells (CD4+ T reg cells), Foxp3- CD8+ regulatory T cells (CD8+ T reg cells) are critical to maintain immune tolerance. However, the molecular programs that specifically control CD8+ but not CD4+ T reg cells are largely unknown. Here, we demonstrate that simultaneous disruption of both TGF-β receptor and transcription factor Eomesodermin (Eomes) in T cells results in lethal autoimmunity due to a specific defect in CD8+ but not CD4+ T reg cells. Further, TGF-β signal maintains the regulatory identity, while Eomes controls the follicular location of CD8+ T reg cells. Both TGF-β signal and Eomes coordinate to promote the homeostasis of CD8+ T reg cells. Together, we have identified a unique molecular program designed for CD8+ T reg cells.

Publication types

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

MeSH terms

  • Animals
  • Autoimmune Diseases / genetics
  • Autoimmune Diseases / immunology*
  • Autoimmune Diseases / pathology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / pathology
  • Mice
  • Mice, Transgenic
  • Signal Transduction / genetics
  • Signal Transduction / immunology*
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / immunology*
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / pathology
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / immunology*

Substances

  • Eomes protein, mouse
  • T-Box Domain Proteins
  • Transforming Growth Factor beta