Congruent effects of estrogen and T-cell receptor peptide therapy on regulatory T cells in EAE and MS

Int Rev Immunol. 2005 Sep-Dec;24(5-6):447-77. doi: 10.1080/08830180500371462.


Both estrogen (E2) and T-cell receptor (TCR) peptides have beneficial effects on the clinical course of experimental autoimmune encephalomyelitis (EAE) and possibly multiple sclerosis (MS) that involve distinct but congruent mechanisms. Of interest, these two approaches share an ability to enhance expression of the FoxP3 gene and associated activity of regulatory T (Treg) cells. E2 increases the number and activity of FoxP3(+) T cells through Esr-1 signaling during TCR activation of CD4(+)CD25(-) T cells. In contrast, TCR peptide therapy appears to increase the frequency of regulatory FoxP3(+) T cells specific for self-TCR determinants expressed by targeted pathogenic T cells. The combined effects on Treg expansion and activation induced by these distinct immunoregulatory approaches may account for their potent effects on clinical EAE and argue for a similar combined therapeutic approach for MS.

Publication types

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

MeSH terms

  • Animals
  • Encephalomyelitis, Autoimmune, Experimental / drug therapy*
  • Encephalomyelitis, Autoimmune, Experimental / genetics
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Estrogens / immunology
  • Estrogens / pharmacology
  • Estrogens / therapeutic use*
  • Female
  • Forkhead Transcription Factors / genetics
  • Gene Expression / drug effects
  • Humans
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Male
  • Models, Immunological
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / genetics
  • Multiple Sclerosis / immunology
  • Peptides / immunology
  • Peptides / therapeutic use
  • Pregnancy
  • Receptors, Antigen, T-Cell / immunology*
  • Receptors, Estrogen / physiology
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology*


  • Estrogens
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Peptides
  • Receptors, Antigen, T-Cell
  • Receptors, Estrogen