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: Sho Takizawa, Tomoki Kaneyama, Sayaka Tsugane, Naoya Takeichi, Satoshi Yanagisawa, Motoki Ichikawa, Hideo Yagita, Byung S Kim, Chang-Sung Koh
• Journal: Journal of neuroimmunology (J Neuroimmunol) Vol. 274 Issue 1-2 Pg. 78-85 (Sep 15 2014) ISSN: 1872-8421 [Electronic] Netherlands
• PMID: 25027060 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

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

Topics

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