Impaired regulatory function in circulating CD4(+)CD25(high)CD127(low/-) T cells in patients with myasthenia gravis

Clin Immunol. 2012 Dec;145(3):209-23. doi: 10.1016/j.clim.2012.09.012. Epub 2012 Oct 7.

Abstract

Previous studies have reported alterations in numbers or function of regulatory T (Treg) cells in myasthenia gravis (MG) patients, but published results have been inconsistent, likely due to the isolation of heterogenous "Treg" populations. In this study, we used surface CD4, CD25(high), and CD127(low/-) expression to isolate a relatively pure population of Tregs, and established that there was no alteration in the relative numbers of Tregs within the peripheral T cell pool in MG patients. In vitro proliferation assays, however, demonstrated that Treg-mediated suppression of responder T (Tresp) cells was impaired in MG patients and was associated with a reduced expression of FOXP3 in isolated Tregs. Suppression of both polyclonal and AChR-activated Tresp cells from MG patients could be restored using Tregs isolated from healthy controls, indicating that the defect in immune regulation in MG is primarily localized to isolated Treg cells, and revealing a potential novel therapeutic target.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Antigen-Presenting Cells / immunology
  • CD4 Antigens / metabolism
  • Case-Control Studies
  • Cell Separation
  • Cytokines / biosynthesis
  • Female
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism
  • Humans
  • In Vitro Techniques
  • Interleukin-10 / biosynthesis
  • Interleukin-2 Receptor alpha Subunit / metabolism
  • Interleukin-7 Receptor alpha Subunit / metabolism
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • Myasthenia Gravis / genetics
  • Myasthenia Gravis / immunology*
  • Myasthenia Gravis / metabolism
  • Receptors, Cholinergic / immunology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism
  • Young Adult

Substances

  • CD4 Antigens
  • Cytokines
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • IL10 protein, human
  • IL2RA protein, human
  • Interleukin-2 Receptor alpha Subunit
  • Interleukin-7 Receptor alpha Subunit
  • Receptors, Cholinergic
  • Interleukin-10