CD4 T cells control development and maintenance of brain-resident CD8 T cells during polyomavirus infection

Taryn E. Mockus, Shwetank, Matthew D. Lauver, Heather M. Ren, Colleen S. Netherby, Tarik Salameh, Yuka Imamura, Feng Yue, James Broach, Aron Lukacher

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Tissue-resident memory CD8 T (T RM ) cells defend against microbial reinfections at mucosal barriers; determinants driving durable T RM cell responses in non-mucosal tissues, which often harbor opportunistic persistent pathogens, are unknown. JC polyomavirus (JCPyV) is a ubiquitous constituent of the human virome. With altered immunological status, JCPyV can cause the oft-fatal brain demyelinating disease progressive multifocal leukoencephalopathy (PML). JCPyV is a human-only pathogen. Using the mouse polyomavirus (MuPyV) encephalitis model, we demonstrate that CD4 T cells regulate development of functional antiviral brain-resident CD8 T cells (bT RM ) and renders their maintenance refractory to systemic CD8 T cell depletion. Acquired CD4 T cell deficiency, modeled by delaying systemic CD4 T cell depletion until MuPyV-specific CD8 T cells have infiltrated the brain, impacted the stability of CD8 bT RM , impaired their effector response to reinfection, and rendered their maintenance dependent on circulating CD8 T cells. This dependence of CD8 bT RM differentiation on CD4 T cells was found to extend to encephalitis caused by vesicular stomatitis virus. Together, these findings reveal an intimate association between CD4 T cells and homeostasis of functional bT RM to CNS viral infection.

Original languageEnglish (US)
Article numbere1007365
JournalPLoS Pathogens
Volume14
Issue number10
DOIs
StatePublished - Oct 1 2018

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Polyomavirus Infections
Maintenance
T-Lymphocytes
Brain
JC Virus
Polyomavirus
Encephalitis
Central Nervous System Viral Diseases
Progressive Multifocal Leukoencephalopathy
Vesicular Stomatitis
Brain Diseases
Demyelinating Diseases
Antiviral Agents
Homeostasis

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

Cite this

Mockus, Taryn E. ; Shwetank ; Lauver, Matthew D. ; Ren, Heather M. ; Netherby, Colleen S. ; Salameh, Tarik ; Imamura, Yuka ; Yue, Feng ; Broach, James ; Lukacher, Aron. / CD4 T cells control development and maintenance of brain-resident CD8 T cells during polyomavirus infection. In: PLoS Pathogens. 2018 ; Vol. 14, No. 10.
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CD4 T cells control development and maintenance of brain-resident CD8 T cells during polyomavirus infection. / Mockus, Taryn E.; Shwetank; Lauver, Matthew D.; Ren, Heather M.; Netherby, Colleen S.; Salameh, Tarik; Imamura, Yuka; Yue, Feng; Broach, James; Lukacher, Aron.

In: PLoS Pathogens, Vol. 14, No. 10, e1007365, 01.10.2018.

Research output: Contribution to journalArticle

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AU - Lukacher, Aron

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