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Volume 34 Issue 5
October 2019
    Citation: Fang Zhang, Linlin Qi, Tong Li, Xiaojing Li, Dan Yang, Shengbo Cao, Jing Ye, Bin Wei. PD1+CCR2+CD8+ T Cells Infiltrate the Central Nervous System during Acute Japanese Encephalitis Virus Infection .VIROLOGICA SINICA, 2019, 34(5) : 538-548.  http://dx.doi.org/10.1007/s12250-019-00134-z
    shu

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

    • 1.

      State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China

    • 2.

      University of Chinese Academy of Science, Beijing 100049, China

    • 3.

      State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China

    • 4.

      School of Life Sciences, Shanghai University, Shanghai 200444, China

    • Corresponding author: Jing Ye, yej@mail.hzau.edu.cn, ORCID: http://orcid.org/0000-0002-3258-6224
      Bin Wei, weibinwhy@shu.edu.cn, ORCID: http://orcid.org/0000-0001-8970-3615
    • Received Date: 25 February 2019
      Accepted Date: 08 April 2019
      Published Date: 18 June 2019
      Available online: 01 October 2019
    • 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 CCR2-CD8+ 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.
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      PD1+CCR2+CD8+ T Cells Infiltrate the Central Nervous System during Acute Japanese Encephalitis Virus Infection

        Corresponding author: Jing Ye, yej@mail.hzau.edu.cn
        Corresponding author: Bin Wei, weibinwhy@shu.edu.cn
      • 1. State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China
      • 2. University of Chinese Academy of Science, Beijing 100049, China
      • 3. State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China
      • 4. School of Life Sciences, Shanghai University, Shanghai 200444, China
      • Received Date: 25 February 2019
      • Accepted Date: 08 April 2019
      • Published Date: 18 June 2019

      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 CCR2-CD8+ 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.

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