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 Kawasawa, Feng Yue, James R. Broach, Aron E. Lukacher

Research output: Contribution to journalArticle

4 Scopus citations

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 2018

All Science Journal Classification (ASJC) codes

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

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