Publication

PD-1 Dynamically Regulates Inflammation and Development of Brain-Resident Memory CD8 T Cells During Persistent Viral Encephalitis

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Last modified
  • 05/22/2025
Type of Material
Authors
    Verma Shwetank, Penn State College of MedicineElizabeth L. Frost, Emory UniversityTaryn E. Mockus, Penn State College of MedicineHeather M. Ren, Penn State College of MedicineMesut Toprak, Yale School of MedicineMatthew D. Lauver, Penn State College of MedicineColleen S. Netherby-Winslow, Penn State College of MedicineGe Jin, Penn State College of MedicineJennifer M. Cosby, University of UtahBrian Evavold, Emory UniversityAron E. Lukacher, Penn State College of Medicine
Language
  • English
Date
  • 2019-04-17
Publisher
  • Frontiers Media
Publication Version
Copyright Statement
  • Copyright © 2019 Shwetank, Frost, Mockus, Ren, Toprak, Lauver, Netherby-Winslow, Jin, Cosby, Evavold and Lukacher.
License
Final Published Version (URL)
Title of Journal or Parent Work
ISSN
  • 1664-3224
Volume
  • 10
Issue
  • MAR
Start Page
  • 783
End Page
  • 783
Grant/Funding Information
  • Funding for this work was supported by grants from The National Institutes of Health (R01 NS088367 and R01 NS092662 to AL, R01 AI096879 to BE, F31 NS083336 to EF, and F32 NS106730 to CN-W); and the Young Investigator Award from Adaptive Biotech Inc. to Shwetank.
Supplemental Material (URL)
Abstract
  • Programmed cell death-1 (PD-1) receptor signaling dampens the functionality of T cells faced with repetitive antigenic stimulation from chronic infections or tumors. Using intracerebral (i.c.) inoculation with mouse polyomavirus (MuPyV), we have shown that CD8 T cells establish a PD-1hi, tissue-resident memory population in the brains (bTRM) of mice with a low-level persistent infection. In MuPyV encephalitis, PD-L1 was expressed on infiltrating myeloid cells, microglia and astrocytes, but not on oligodendrocytes. Engagement of PD-1 on anti-MuPyV CD8 T cells limited their effector activity. NanoString gene expression analysis showed that neuroinflammation was higher in PD-L1−/− than wild type mice at day 8 post-infection, the peak of the MuPyV-specific CD8 response. During the persistent phase of infection, however, the absence of PD-1 signaling was found to be associated with a lower inflammatory response than in wild type mice. Genetic disruption and intracerebroventricular blockade of PD-1 signaling resulted in an increase in number of MuPyV-specific CD8 bTRM and the fraction of these cells expressing CD103, the αE integrin commonly used to define tissue-resident T cells. However, PD-L1−/− mice persistently infected with MuPyV showed impaired virus control upon i.c. re-infection with MuPyV. Collectively, these data reveal a temporal duality in PD-1-mediated regulation of MuPyV-associated neuroinflammation. PD-1 signaling limited the severity of neuroinflammation during acute infection but sustained a level of inflammation during persistent infection for maintaining control of virus re-infection.
Author Notes
Keywords
Research Categories
  • Biology, Neuroscience
  • Health Sciences, Immunology
  • Biology, Virology

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