Promiscuous gene expression in medullary thymic epithelial cells mirrors the peripheral self

Nat Immunol. 2001 Nov;2(11):1032-9. doi: 10.1038/ni723.

Abstract

Expression of peripheral antigens in the thymus has been implicated in T cell tolerance and autoimmunity. Here we identified medullary thymic epithelial cells as being a unique cell type that expresses a diverse range of tissue-specific antigens. We found that this promiscuous gene expression was a cell-autonomous property of medullary epithelial cells and was maintained during the entire period of thymic T cell output. It may facilitate tolerance induction to self-antigens that would otherwise be temporally or spatially secluded from the immune system. However, the array of promiscuously expressed self-antigens appeared random rather than selected and was not confined to secluded self-antigens.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantigens / biosynthesis*
  • Autoantigens / genetics
  • Autoantigens / immunology
  • Bone Marrow Transplantation
  • Cells, Cultured / metabolism
  • DNA, Complementary / genetics
  • DNA-Binding Proteins / deficiency
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology
  • Epithelial Cells / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Inbred NOD
  • Mice, Transgenic
  • Organ Specificity
  • Radiation Chimera
  • Reverse Transcriptase Polymerase Chain Reaction
  • Self Tolerance / genetics*
  • Serum Amyloid P-Component / biosynthesis
  • Serum Amyloid P-Component / deficiency
  • Serum Amyloid P-Component / genetics
  • Specific Pathogen-Free Organisms
  • Spleen / cytology
  • Spleen / metabolism
  • Stromal Cells / metabolism
  • T-Lymphocyte Subsets / immunology*
  • Testis / cytology
  • Testis / metabolism
  • Thymus Gland / cytology
  • Thymus Gland / embryology
  • Thymus Gland / metabolism*
  • Thymus Gland / transplantation
  • Transcription Factors / metabolism

Substances

  • Autoantigens
  • DNA, Complementary
  • DNA-Binding Proteins
  • Rag2 protein, mouse
  • Serum Amyloid P-Component
  • Transcription Factors
  • V(D)J recombination activating protein 2