title: Role of the Programmed Death-1 (PD-1) pathway in regulation of Theiler's murine encephalomyelitis virus-induced demyelinating disease.
abstract: Programmed death-1 (PD-1) belongs to the CD28 family of co-stimulatory and co-inhibitory molecules and regulates adaptive immunity. This molecule induces the development of regulatory T cells, T cell tolerance, or apoptosis. We examined the role of PD-1 pathway in Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease (TMEV-IDD) mice. Up-regulation of PD-1 and PD-1 ligand-1 (PD-L1) mRNA expression in bone marrow-derived dendritic cells were induced by TMEV infection in vitro. Furthermore, PD-1 and PD-L1 mRNA expression was increased in the spinal cords of the TMEV-infected mice in vivo. Treatment with a blocking monoclonal antibody (mAb) against PD-1, especially during the effector phase, resulted in significant deterioration of the TMEV-IDD both clinically and histologically. Flow cytometric analysis revealed a dramatically increase of CD4(+) T cells producing Th1 cytokines such as IFN-γ and TNF-α in the spinal cord of anti-PD-1 mAb-treated mice. These results indicate that the PD-1 pathway plays a pivotal regulatory role in the development of TMEV-IDD.
authors.affiliation: Department of Biomedical Laboratory Sciences, Graduate School of Medicine, Shinshu University, Matsumoto, Nagano 390-8621, Japan.
authors.forename: Sho
authors.initials: S
authors.lastname: Takizawa
authors.affiliation: Department of Biomedical Laboratory Sciences, Graduate School of Medicine, Shinshu University, Matsumoto, Nagano 390-8621, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Kaneyama
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.affiliation: Department of Biomedical Laboratory Sciences, Graduate School of Medicine, Shinshu University, Matsumoto, Nagano 390-8621, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Takeichi
authors.affiliation: Department of Biomedical Laboratory Sciences, Graduate School of Medicine, Shinshu University, Matsumoto, Nagano 390-8621, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yanagisawa
authors.affiliation: Department of Biomedical Laboratory Sciences, Graduate School of Medicine, Shinshu University, Matsumoto, Nagano 390-8621, Japan.
authors.forename: Motoki
authors.initials: M
authors.lastname: Ichikawa
authors.affiliation: Department of Immunology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Yagita
authors.affiliation: Department of Microbiology-Immunology, Northwestern University Finberg Medical School, 303 East Chicago Avenue, Chicago, IL 60611, USA.
authors.forename: Byung S
authors.initials: BS
authors.lastname: Kim
authors.affiliation: Department of Biomedical Laboratory Sciences, Graduate School of Medicine, Shinshu University, Matsumoto, Nagano 390-8621, Japan. Electronic address: kshosei@shinshu-u.ac.jp.
authors.forename: Chang-Sung
authors.initials: CS
authors.lastname: Koh
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000276:immunology / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D060890:B7-H1 Antigen / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D006224:Cricetinae; D003711:Demyelinating Diseases / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D007668:Kidney / Q000166:cytology; D051379:Mice; D008815:Mice, Inbred Strains; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D013116:Spinal Cord / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D017945:Theilovirus / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
chemical_list: D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma
keywords: Demyelination; Multiple sclerosis (MS); PD-L1; Programmed Death-1 (PD-1); Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD)