Role of the Programmed Death-1 (PD-1) pathway in regulation of Theiler's murine encephalomyelitis virus-induced demyelinating disease

Sho Takizawa, Tomoki Kaneyama, Sayaka Tsugane, Naoya Takeichi, Satoshi Yanagisawa, Motoki Ichikawa, Hideo Yagita, Byung S. Kim, Chang Sung Koh*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)78-85
Number of pages8
JournalJournal of Neuroimmunology
Volume274
Issue number1-2
DOIs
StatePublished - 2014

Keywords

  • Demyelination
  • Multiple sclerosis (MS)
  • PD-L1
  • Programmed Death-1 (PD-1)
  • Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD)

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

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