Large functional repertoire of regulatory T-cell suppressible autoimmune T cells in scurfy mice

J Autoimmun. 2007 Aug;29(1):10-9. doi: 10.1016/j.jaut.2007.04.001. Epub 2007 May 23.

Abstract

Scurfy mice which lacks functional Foxp3 transcription factor and CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells, spontaneously develop autoimmune responses against skin, lung, liver and tail. However, many organs/tissues are spared from autoimmune attack. Here, we demonstrate that scurfy mice contain dormant autoimmune T cells that induced new diseases such as sialoadenitis, dacryoadenitis, pancreatitis, gastritis, intestinal inflammation, colitis, and myositis in RAG-1 KO mice. Inflammation in as many as 12 organs/tissues was consistently induced in individual recipients with scurfy lymph node cells containing as few as 1.25 x 10(6) CD4(+) T cells. Moreover, transfer of the multiple organ autoimmune diseases could be suppressed by as little as 0.5 x 10(6) CD4(+)CD25(+) Treg cells, mediated by inhibiting autoimmune T-cell expansion. Our study provides evidence for the presence of a large repertoire of autoimmune lymphocytes against various organs/tissues in scurfy mice as well as Treg cells in B6 mice capable of suppressing the expansion of these autoimmune lymphocytes. Various conditions that control the expression of autoimmune T cells are discussed.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Autoimmune Diseases / immunology*
  • Autoimmune Diseases / pathology
  • Autoimmunity
  • CD4 Antigens / analysis
  • Female
  • Forkhead Transcription Factors / analysis
  • Homeodomain Proteins / genetics
  • Immune Tolerance*
  • Inflammation / immunology
  • Inflammation / pathology
  • Interleukin-2 Receptor alpha Subunit / analysis
  • Male
  • Mice
  • Mice, Knockout
  • T-Lymphocytes, Regulatory / immunology*

Substances

  • CD4 Antigens
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Homeodomain Proteins
  • Interleukin-2 Receptor alpha Subunit
  • RAG-1 protein