title: Therapeutic effects of anti-Delta1 mAb on Theiler's murine encephalomyelitis virus-induced demyelinating disease.
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.
authors.affiliation: Department of Biomedical Laboratory Sciences, Graduate School of Medicine, Shinshu University, Matsumoto, Nagano 390-8621, Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Tsugane
authors.forename: Sho
authors.initials: S
authors.lastname: Takizawa
authors.forename: Tomoki
authors.initials: T
authors.lastname: Kaneyama
authors.forename: Motoki
authors.initials: M
authors.lastname: Ichikawa
authors.forename: Hideo
authors.initials: H
authors.lastname: Yagita
authors.forename: Byung S
authors.initials: BS
authors.lastname: Kim
authors.forename: Chang-Sung
authors.initials: CS
authors.lastname: Koh
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D018188:Cardiovirus Infections / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D003711:Demyelinating Diseases / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D005260:Female; D005434:Flow Cytometry; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors* / Q000276:immunology; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000276:immunology; D051379:Mice; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000473:pathology; D017945:Theilovirus
chemical_list: D000911:Antibodies, Monoclonal; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C064045:delta protein