Regulatory function of CD4+CD25++ T cells in patients with myasthenia gravis is associated with phenotypic changes and STAT5 signaling: 1,25-Dihydroxyvitamin D3 modulates the suppressor activity

J Neuroimmunol. 2015 Apr 15:281:51-60. doi: 10.1016/j.jneuroim.2015.03.008. Epub 2015 Mar 10.

Abstract

Regulatory T cells were investigated in early-onset (EO) and late-onset (LO) myasthenia gravis patients with anti-acetylcholine receptor antibody (AChR-MG). Alterations in PD-1 and PD-L1 on CD4(+)CD25(++) (Treg) and responder T cells (Tresp, CD4(+)CD25(-)) were observed in LOMG patients. GITR was decreased on CD4(+)CD25(++) of all patients. Decrease of FOXP3 was associated with lower phosphorylation of STAT5.1,25-dihydroxyvitamin D3 (VitD3) increased suppression in co-culture with a stronger effect in patients by acting possibly both on cell groups. Changes in surface molecules and intracellular pathways contribute to the defects of Treg in non-thymomatous AChR-MG and VitD3 can have modulatory effects.

Keywords: GITR; LOMG; PD-1; STAT-5; Treg; Vitamin D.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • CD4-Positive T-Lymphocytes / physiology*
  • Calcitriol / pharmacology*
  • Cells, Cultured
  • Coculture Techniques
  • Female
  • Humans
  • Interleukin-2 Receptor alpha Subunit / physiology*
  • Male
  • Middle Aged
  • Myasthenia Gravis / metabolism*
  • Phenotype*
  • STAT5 Transcription Factor / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Young Adult

Substances

  • IL2RA protein, human
  • Interleukin-2 Receptor alpha Subunit
  • STAT5 Transcription Factor
  • Calcitriol