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PD1+CCR2+CD8+ T Cells Infiltrate the Central Nervous System during Acute Japanese Encephalitis Virus Infection

  • Fang Zhang
  • Linlin Qi
  • Tong Li
  • Xiaojing Li
  • Dan Yang
  • Shengbo Cao
  • Jing YeEmail author
  • Bin WeiEmail author
Research Article
  • 55 Downloads

Abstract

Japanese encephalitis (JE) is a viral encephalitis disease caused by Japanese encephalitis virus (JEV) infection. Uncontrolled inflammatory responses in the central nervous system (CNS) are a hallmark of severe JE. Although the CCR2–CCL2 axis is important for monocytes trafficking during JEV infection, little is known about its role in CNS trafficking of CD8+ T cells. Here, we characterized a mouse model of JEV infection, induced via intravenous injection (i.v.) and delineated the chemokines and infiltrating peripheral immune cells in the brains of infected mice. The CNS expression of chemokines, Ccl2, Ccl3, and Ccl5, and their receptors, Ccr2 or Ccr5, was significantly up-regulated after JEV infection and was associated with the degree of JE pathogenesis. Moreover, JEV infection resulted in the migration of a large number of CD8+ T cells into the CNS. In the brains of JEV-infected mice, infiltrating CD8+ T cells expressed CCR2 and CCR5 and were found to comprise mainly effector T cells (CD44+CD62L). JEV infection dramatically enhanced the expression of programmed death 1 (PD-1) on infiltrating CD8+ T cells in the brain, as compared to that on peripheral CD8+ T cells in the spleen. This effect was more pronounced on infiltrating CCR2+CD8+ T cells than on CCR2CD8+ T cells. In conclusion, we identified a new subset of CD8+ T cells (PD1+CCR2+CD8+ T cells) present in the CNS of mice during acute JEV infection. These CD8+ T cells might play a role in JE pathogenesis.

Keywords

Japanese encephalitis virus (JEV) CD8+ T cell CCL2 CCR2 PD-1 

Notes

Acknowledgements

This work was supported by grants from the Key Research and Development Program of the Ministry of Science and Technology of China (2016YFD500407), Precision Medicine program of Ministry of Science and Technology of China (2016YFC0905902), and the National Natural Science Foundation of China (81630043, 81571552). We thank the Core Facility and Technical Support in the Wuhan Investigate of Virology. We are grateful to Ding Gao and Juan Min for technical support for flow cytometry and mass cytometry, as well as Xuefang An and Fan Zhang for valuable assistance in the animal studies.

Author Contributions

BW and JY conceptualized and designed the study. LLQ, TL and FZ performed the experiments in this study, and analyzed the data. SBC and JY contributed virus strain and virus infection techniques to this study. DY and XJL participated in part of experimental work. FZ wrote the manuscript. All authors read and approved the final manuscript.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Animal and Human Rights Statement

The study was approved by the Animal Ethics Committee of Wuhan Institute of Virology. All institutional and national guidelines for the care and use of laboratory animals were followed.

Supplementary material

12250_2019_134_MOESM1_ESM.pdf (488 kb)
Supplementary material 1 (PDF 489 kb)

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Copyright information

© Wuhan Institute of Virology, CAS 2019

Authors and Affiliations

  1. 1.State Key Laboratory of Virology, Wuhan Institute of VirologyChinese Academy of SciencesWuhanChina
  2. 2.University of Chinese Academy of ScienceBeijingChina
  3. 3.State Key Laboratory of Agricultural MicrobiologyHuazhong Agricultural UniversityWuhanChina
  4. 4.School of Life SciencesShanghai UniversityShanghaiChina

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