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

J Neuroimmunol. 2014 Sep 15;274(1-2):78-85. doi: 10.1016/j.jneuroim.2014.06.018. Epub 2014 Jun 27.

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.

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Blocking / immunology
  • Antibodies, Blocking / pharmacology
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacology
  • B7-H1 Antigen / genetics
  • B7-H1 Antigen / immunology*
  • B7-H1 Antigen / metabolism
  • Cell Line
  • Cricetinae
  • Demyelinating Diseases / immunology*
  • Demyelinating Diseases / metabolism
  • Demyelinating Diseases / virology
  • Dendritic Cells / immunology
  • Female
  • Flow Cytometry
  • Gene Expression / immunology
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Kidney / cytology
  • Mice
  • Mice, Inbred Strains
  • Programmed Cell Death 1 Receptor / genetics
  • Programmed Cell Death 1 Receptor / immunology*
  • Programmed Cell Death 1 Receptor / metabolism
  • Spinal Cord / immunology*
  • Th1 Cells / immunology
  • Theilovirus / immunology*
  • Tumor Necrosis Factor-alpha / immunology
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antibodies, Blocking
  • Antibodies, Monoclonal
  • B7-H1 Antigen
  • Cd274 protein, mouse
  • Pdcd1 protein, mouse
  • Programmed Cell Death 1 Receptor
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma