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

• Published in: Journal of neuroimmunology 2012-11, Vol.252 (1), p.66-74
• Main Authors: Tsugane, Sayaka, Takizawa, Sho, Kaneyama, Tomoki, Ichikawa, Motoki, Yagita, Hideo, Kim, Byung S, Koh, Chang-Sung
• Format: Article
• Language: English
• Subjects: Allergy and Immunology; Animals; Antibodies, Monoclonal - pharmacology; Cardiovirus Infections - drug therapy; Cardiovirus Infections - pathology; Cardiovirus Infections - virology; CD4 antigen; Data processing; Delta protein; Delta-like 1 (Delta1); Demyelinating disease; Demyelinating diseases; Demyelinating Diseases - drug therapy; Demyelinating Diseases - pathology; Demyelinating Diseases - virology; Encephalomyelitis; Female; Flow Cytometry; gamma -Interferon; Inflammation; Intracellular Signaling Peptides and Proteins - antagonists & inhibitors; Intracellular Signaling Peptides and Proteins - immunology; Leukocytes (mononuclear); Membrane Proteins - antagonists & inhibitors; Membrane Proteins - immunology; Mice; Monoclonal antibodies; Multiple sclerosis; Multiple sclerosis (MS); Neurology; Notch protein; Notch signaling; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; Spinal cord; Spinal Cord - pathology; Spleen; Splenocytes; Theiler's encephalomyelitis virus; Theiler's murine encephalomyelitis virus (TMEV); Theilovirus
• ISSN: 0165-5728; 1872-8421
• DOI: 10.1016/j.jneuroim.2012.08.003

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.