CD4+CD25+FoxP3+ T lymphocytes fail to suppress myelin basic protein-induced proliferation in patients with multiple sclerosis

J Neuroimmunol. 2006 Nov;180(1-2):178-84. doi: 10.1016/j.jneuroim.2006.08.003. Epub 2006 Sep 29.

Abstract

Multiple sclerosis (MS) is an autoimmune disorder directed against self antigens of the central nervous system. CD4(+)CD25(+)FoxP3(+) regulatory T cell (T(reg)) mediated suppression is an essential mechanism of self-tolerance. We studied whether changes in the suppressive function of a mixture of CD25(high) and CD25(intemediate) expressing T(reg) cells in myelin basic protein (MBP)-induced proliferation occurred in untreated MS patients. Suppression of MBP-induced proliferation was observed in 13 out of 29 (45%) MS patients; this was significantly (p<0.05) less compared with 17 out of 19 (89%) healthy individuals. Relative T(reg) counts was significantly increased in MS patients (mean+/-S.D.; 20+/-8%) compared with healthy individuals (15+/-5%). These findings suggest that impaired T(reg) function may be involved in pathogenesis of MS.

MeSH terms

  • Adult
  • Aged
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Count
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Female
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / immunology*
  • Humans
  • Immune Tolerance / immunology*
  • Immunity, Cellular / drug effects
  • Immunity, Cellular / immunology
  • Interleukin-2 Receptor alpha Subunit / immunology*
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Male
  • Middle Aged
  • Multiple Sclerosis / immunology*
  • Multiple Sclerosis / physiopathology
  • Myelin Basic Protein / immunology
  • Myelin Basic Protein / pharmacology
  • RNA, Messenger / drug effects
  • RNA, Messenger / immunology
  • RNA, Messenger / metabolism
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology
  • Up-Regulation / drug effects
  • Up-Regulation / immunology

Substances

  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Interleukin-2 Receptor alpha Subunit
  • Myelin Basic Protein
  • RNA, Messenger