Therapeutic effects of anti-Delta1 mAb on Theiler's murine encephalomyelitis virus-induced demyelinating disease

J Neuroimmunol. 2012 Nov 15;252(1-2):66-74. doi: 10.1016/j.jneuroim.2012.08.003. Epub 2012 Aug 31.

Abstract

We examined the role of Notch ligand Delta-like 1 (Delta1) in the development of Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease (TMEV-IDD). Blocking of Delta1 by anti-Delta1 monoclonal antibody (mAb) in the effector phase significantly suppressed the disease development of TMEV-IDD both clinically and histologically. The number of infiltrating inflammatory mononuclear cells in the spinal cords was also decreased in mice treated with anti-Delta1 mAb at the effector phase. Flow cytometric analysis of cytokine staining revealed that IFN-γ- or IL-4-producing CD4(+) splenocytes were significantly decreased in mice treated with anti-Delta1 mAb in the spleens, whereas IL-10-producing CD4(+) splenocytes were increased. Furthermore, IFN-γ-, TNF-α-, IL-4-, or IL-10-producing CD4(+) cells were decreased in spinal cords, and IL-17-producing CD4(+) cells were increased. These data suggest that Delta1 may play important roles in the development of TMEV-IDD and that antibodies to Delta1 could be used as a novel therapeutic treatment of demyelinating diseases such as human multiple sclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology*
  • Cardiovirus Infections / drug therapy*
  • Cardiovirus Infections / pathology
  • Cardiovirus Infections / virology
  • Demyelinating Diseases / drug therapy*
  • Demyelinating Diseases / pathology
  • Demyelinating Diseases / virology
  • Female
  • Flow Cytometry
  • Intracellular Signaling Peptides and Proteins / antagonists & inhibitors*
  • Intracellular Signaling Peptides and Proteins / immunology
  • Membrane Proteins / antagonists & inhibitors*
  • Membrane Proteins / immunology
  • Mice
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Spinal Cord / pathology
  • Theilovirus

Substances

  • Antibodies, Monoclonal
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • delta protein