Beneficial effect of tolerogenic dendritic cells pulsed with MOG autoantigen in experimental autoimmune encephalomyelitis

CNS Neurosci Ther. 2015 Mar;21(3):222-30. doi: 10.1111/cns.12342. Epub 2014 Nov 18.

Abstract

Background: Treatment with tolerogenic dendritic cells (TolDC) is a promising, cell-based strategy to regulate autoimmune diseases such as multiple sclerosis (MS) in an antigen-specific way. This technique involves the use of TolDC from MS patients cultured in the presence of vitamin D(3) (VitD3) and pulsed with myelin peptides to induce a stable hyporesponsiveness in myelin-specific autologous T cells.

Aim: The purpose of this study was to analyze the in vivo effect of VitD3-TolDC treatment on experimental autoimmune encephalomyelitis, an animal model of MS.

Methods: Bone marrow-derived TolDC cultured in the presence of VitD3 and pulsed with peptide 40-55 of the myelin oligodendrocyte glycoprotein (MOG(40-55)) were administrated preventively, preclinically, and therapeutically to EAE-induced mice.

Results: We found that VitD3-TolDC-MOG treatment showed a beneficial effect, not only decreasing the incidence of the disease but also reducing the severity of the clinical signs mediated by induction of regulatory T cells (Treg), as well as IL-10 production and reduction of Ag-specific lymphoproliferation. Our results support VitD3-TolDC-peptide(s) treatment as a potential strategy to restore tolerance in autoimmune diseases such as MS.

Keywords: Dendritic cells; Experimental autoimmune encephalomyelitis; Regulatory T cells; Tolerance; Vitamin D3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantigens / metabolism*
  • Bone Marrow Cells / physiology
  • Cell Culture Techniques
  • Cell Movement / physiology
  • Cell Transplantation / methods*
  • Cells, Cultured
  • Cholecalciferol / metabolism
  • Dendritic Cells / pathology
  • Dendritic Cells / physiology
  • Dendritic Cells / transplantation*
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Encephalomyelitis, Autoimmune, Experimental / physiopathology
  • Encephalomyelitis, Autoimmune, Experimental / therapy*
  • Female
  • Interleukin-10 / metabolism
  • Mice, Inbred C57BL
  • Myelin-Oligodendrocyte Glycoprotein / immunology*
  • Severity of Illness Index
  • Spleen / pathology
  • Spleen / physiopathology
  • T-Lymphocytes, Regulatory / physiology

Substances

  • Autoantigens
  • IL10 protein, mouse
  • Mog protein, mouse
  • Myelin-Oligodendrocyte Glycoprotein
  • Interleukin-10
  • Cholecalciferol