Extrathymic Aire-expressing cells are a distinct bone marrow-derived population that induce functional inactivation of CD4⁺ T cells

Immunity. 2013 Sep 19;39(3):560-72. doi: 10.1016/j.immuni.2013.08.005. Epub 2013 Aug 29.

Abstract

The autoimmune regulator (Aire) is essential for prevention of autoimmunity; its role is best understood in the thymus, where it promotes self-tolerance through tissue-specific antigen (TSA) expression. Recently, extrathymic Aire-expressing cells (eTACs) have been described in murine secondary lymphoid organs, but the identity of such cells and their role in immune tolerance remains unclear. Here we have shown that eTACs are a discrete major histocompatibility complex class II (MHC II)(hi), CD80(lo), CD86(lo), epithelial cell adhesion molecule (EpCAM)(hi), CD45(lo) bone marrow-derived peripheral antigen-presenting cell (APC) population. We also have demonstrated that eTACs can functionally inactivate CD4⁺ T cells through a mechanism that does not require regulatory T cells (Treg) and is resistant to innate inflammatory stimuli. Together, these findings further define eTACs as a distinct tolerogenic cell population in secondary lymphoid organs.

Publication types

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

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antigen Presentation
  • Antigen-Presenting Cells / metabolism
  • Antigens, Neoplasm / metabolism
  • Autoimmunity
  • B7-1 Antigen / metabolism
  • B7-2 Antigen / metabolism
  • Bone Marrow Cells
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Adhesion Molecules / metabolism
  • Epithelial Cell Adhesion Molecule
  • Histocompatibility Antigens Class II / immunology
  • Leukocyte Common Antigens / metabolism
  • Mice
  • Mice, Inbred NOD
  • Self Tolerance*
  • Transcription Factors / biosynthesis
  • Transcription Factors / metabolism*

Substances

  • APECED protein
  • Antigens, Neoplasm
  • B7-1 Antigen
  • B7-2 Antigen
  • Cell Adhesion Molecules
  • Epithelial Cell Adhesion Molecule
  • Histocompatibility Antigens Class II
  • Transcription Factors
  • Leukocyte Common Antigens