CD4+CD25+FoxP3+PD1- regulatory T cells in acute and stable relapsing-remitting multiple sclerosis and their modulation by therapy

FASEB J. 2008 Oct;22(10):3500-8. doi: 10.1096/fj.08-110650. Epub 2008 Jun 27.


The intracellular expression of the programmed death receptor 1 (PD1) identifies a subset of naive T(reg) cells with enhanced suppressive ability; antigen stimulation results in the surface expression of PD1. Because the role of T(reg) impairments in multiple sclerosis (MS) is still contradictory, we analyzed naive PD1- and PD1+ T(reg) cells in peripheral blood and cerebrospinal fluid (CSF) of relapsing-remitting multiple sclerosis (RR-MS) patients and of healthy control subjects. Results showed that 1) CSF PD1- T(reg) cells were significantly augmented in MS patients; 2) PD1- T(reg) cells were significantly increased in the peripheral blood of patients with stable disease (SMS) compared to those with acute (AMS) disease, and in patients responding to glatiramer acetate (COPA) compared to AMS- and COPA-unresponsive patients; and 3) PD1+ T(reg) cells were similar in CSF and peripheral blood of all groups analyzed. PD1- T(reg) cells were not increased in the peripheral blood of interferon-beta (IFNbeta) -responsive patients, but the suppressive ability of T(reg) cells was significantly higher in SMS and in COPA- or IFNbeta-responsive compared to AMS- and COPA-unresponsive individuals. The data herein suggest that PD1- T(reg) cells play a pivotal role in MS and offer a biological explanation for disease relapse and for the mechanism associated with response to COPA and IFNbeta.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD / biosynthesis
  • Apoptosis Regulatory Proteins / biosynthesis
  • CD4 Antigens / immunology
  • Cerebrospinal Fluid / immunology
  • Disease Progression
  • Female
  • Forkhead Transcription Factors / immunology
  • Glatiramer Acetate
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Interferon-gamma / therapeutic use
  • Interleukin-2 Receptor alpha Subunit / immunology
  • Male
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Multiple Sclerosis, Relapsing-Remitting / immunology*
  • Myelin Basic Protein / metabolism
  • Peptides / therapeutic use
  • Programmed Cell Death 1 Receptor
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology*


  • Antigens, CD
  • Apoptosis Regulatory Proteins
  • CD4 Antigens
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Immunosuppressive Agents
  • Interleukin-2 Receptor alpha Subunit
  • Myelin Basic Protein
  • PDCD1 protein, human
  • Peptides
  • Programmed Cell Death 1 Receptor
  • Glatiramer Acetate
  • Interferon-gamma