CD127 immunophenotyping suggests altered CD4+ T cell regulation in primary progressive multiple sclerosis

J Autoimmun. 2008 Aug;31(1):52-8. doi: 10.1016/j.jaut.2008.02.003. Epub 2008 Apr 11.

Abstract

Aberrant regulatory T cell populations, characterised by a wide array of CD markers, have been identified in many autoimmune diseases. CD127 has recently been identified as a specific marker for the CD4(+)CD25(Hi) (Tregs) subset. CD127 is the first non-HLA gene to have its association with multiple sclerosis widely replicated. We demonstrate that the regulatory or suppressor T cells CD4(+)CD25(Hi) (Tregs), CD8(+)CD28(-), and CD3(+)CD56(+) (NKT) all produce low levels of CD127, and so could be at a disadvantage in survival and/or proliferation where IL7 is limiting. The remissions seen in relapsing remitting multiple sclerosis (RRMS) could be driven by regulatory T cells, and the absence of remissions seen in primary progressive MS (PPMS) may point to a particularly reduced function of this cell subset. We found that the proportions of CD4(+)FoxP3(+)CD25(Hi) regulatory T cells were not aberrant in PPMS. There was, however, a trend towards reduced FoxP3 expression per cell in this fraction (p<0.083), which has been highly correlated with suppressor function. Notably, we found that the target of regulatory T cells, the CD4(+)CD25(-) cells, was in excess (p<0.009); and in PPMS a protective CD127 haplotype is correlated with higher CD127 expression (p<0.01). These data support further investigations into the regulatory T cell immunophenotype in MS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, Surface / biosynthesis*
  • Antigens, Surface / immunology
  • Cell Separation
  • Female
  • Flow Cytometry
  • Forkhead Transcription Factors / biosynthesis
  • Forkhead Transcription Factors / immunology
  • Humans
  • Immunophenotyping
  • Interleukin-7 Receptor alpha Subunit / biosynthesis*
  • Interleukin-7 Receptor alpha Subunit / immunology
  • Male
  • Middle Aged
  • Multiple Sclerosis, Chronic Progressive / immunology*
  • Multiple Sclerosis, Chronic Progressive / pathology
  • Multiple Sclerosis, Relapsing-Remitting / immunology*
  • Multiple Sclerosis, Relapsing-Remitting / pathology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocyte Subsets / pathology
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism
  • T-Lymphocytes, Regulatory / pathology

Substances

  • Antigens, Surface
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Interleukin-7 Receptor alpha Subunit