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

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.