Decreased FOXP3 levels in multiple sclerosis patients

J Neurosci Res. 2005 Jul 1;81(1):45-52. doi: 10.1002/jnr.20522.


Autoimmune diseases such as multiple sclerosis (MS) may result from the failure of tolerance mechanisms to prevent expansion of pathogenic T cells. Our study is the first to establish that MS patients have abnormalities in FOXP3 message and protein expression levels in peripheral CD4+ CD25+ T cells (Tregs) that are quantitatively related to a reduction in functional suppression induced during suboptimal T-cell receptor (TCR) ligation. Of importance, this observation links a defect in functional peripheral immunoregulation to an established genetic marker that has been unequivocally shown to be involved in maintaining immune tolerance and preventing autoimmune diseases. Diminished FOXP3 levels thus indicate impaired immunoregulation by Tregs that may contribute to MS. Future studies will evaluate the effects of therapies known to influence Treg cell function and FOXP3 expression, including TCR peptide vaccination and supplemental estrogen.

Publication types

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

MeSH terms

  • Adult
  • CD4 Antigens / immunology
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism*
  • Female
  • Forkhead Transcription Factors
  • Genetic Markers / immunology
  • Genetic Markers / physiology
  • Humans
  • Male
  • Middle Aged
  • Multiple Sclerosis / genetics*
  • Multiple Sclerosis / immunology*
  • Multiple Sclerosis / metabolism
  • RNA, Messenger / analysis
  • Receptors, Interleukin-2 / immunology
  • Reference Values
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism*


  • CD4 Antigens
  • DNA-Binding Proteins
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Genetic Markers
  • RNA, Messenger
  • Receptors, Interleukin-2