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

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

Author information

1
Department of Biomedical Laboratory Sciences, Graduate School of Medicine, Shinshu University, Matsumoto, Nagano 390-8621, Japan.
2
Department of Immunology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo 113-8421, Japan.
3
Department of Microbiology-Immunology, Northwestern University Finberg Medical School, 303 East Chicago Avenue, Chicago, IL 60611, USA.
4
Department of Biomedical Laboratory Sciences, Graduate School of Medicine, Shinshu University, Matsumoto, Nagano 390-8621, Japan. Electronic address: kshosei@shinshu-u.ac.jp.

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)

PMID:
25027060
DOI:
10.1016/j.jneuroim.2014.06.018
[Indexed for MEDLINE]

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