GM-CSF production by CD4+ T cells in MS patients: Regulation by regulatory T cells and vitamin D

E. Peelen, A.H. Muris, J. Damoiseaux, S. Knippenberg, K. Broens, J. Smolders, J.W. Tervaert, R. Hupperts, M. Thewissen

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

BACKGROUND/OBJECTIVE: Data from animal models of MS suggest that GM-CSF(+)CD4(+)T cells are pathogenic cells. Therefore, GM-CSF production by CD4(+)T cells of MS patients and their susceptibility to regulatory mechanisms were investigated. METHODS: Intracellular flowcytometry was performed to determine the GM-CSF(+)CD4(+)T cell fraction in PBMC and CSF of MS patients and controls. The effect of regulatory T cells (Tregs) on GM-CSF production by CD4(+)T cells was studied in MS patients using a proliferation-suppression assay. Finally, GM-CSF(+)CD4(+)T cell fraction and GM-CSF protein levels in supernatant were assessed in anti-CD3-stimulated CD4(+)T cell cultures derived from healthy controls and MS patients, in the presence or absence of the active vitamin D metabolite calcitriol. RESULTS: The GM-CSF(+)CD4(+)T cell fraction in the peripheral blood did not differ between controls and MS patients. This T cell population could also be detected in the CSF of both subjects with MS as well as subjects with another diagnosis. In the CSF, it comprised a significant fraction of the T cell population. Upon in vitro stimulation of PBMC with anti-CD3 antibody, no differences were observed in GM-CSF(+)CD4(+)T cell frequencies. GM-CSF secretion was susceptible to regulation by Treg and vitamin D. Suppression of GM-CSF secretion by vitamin D was reduced in MS patients. CONCLUSIONS: Our study showed no elevation in GM-CSF(+)CD4(+)T cell fractions in MS patients compared to controls. Furthermore, GM-CSF secretion was prone to regulation by Treg and vitamin D, the latter being less effective in MS patients.
Original languageEnglish
Pages (from-to)36-42
Number of pages7
JournalJournal of Neuroimmunology
Volume280
DOIs
Publication statusPublished - 15 Mar 2015

Keywords

  • Multiple sclerosis
  • T helper cell
  • GM-CSF
  • Regulatory T cell
  • Vitamin D
  • COLONY-STIMULATING FACTOR
  • MULTIPLE-SCLEROSIS PATIENTS
  • EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS
  • CEREBROSPINAL-FLUID
  • POTASSIUM CHANNEL
  • DENDRITIC CELLS
  • HELPER-CELLS
  • CYTOKINE
  • EXPRESSION
  • INFLAMMATION

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