Rapid formation of extended processes and engagement of Theiler's virus-infected neurons by CNS-infiltrating CD8 T cells

Jeremiah R. McDole, Steve C. Danzer, Raymund Y.K. Pun, Yi Chen, Holly L. Johnson, Istvan Pirko, Aaron J. Johnson

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

A fundamental question in neuroimmunology is the extent to which CD8 T cells actively engage virus-infected neurons. In the Theiler's murine encephalomyelitis virus (TMEV) model of multiple sclerosis, an effective central nervous system (CNS)-infiltrating antiviral CD8 T cell response offers protection from this demyelinating disease. However, the specific CNS cell types engaged by these protective CD8 T cells in TMEV-resistant strains remains unknown. We used confocal microscopy to visualize the morphology, migration, and specific cellular interactions between adoptively transferred CD8 T cells and specific CNS cell types. Adoptively transferred GFP+ CD8+ splenocytes migrated to the brain and became 93% specific for the immunodominant virus epitope Db:VP2121-130. These CD8 T cells also polarized T cell receptor, CD8 protein, and granzyme B toward target neurons. Furthermore, we observed CD8 T cells forming cytoplasmic processes up to 45 μm in length. Using live tissue imaging, we determined that these T cell-extended processes (TCEPs) could be rapidly formed and were associated with migratory behavior through CNS tissues. These studies provide evidence that antiviral CD8 T cells have the capacity to engage virus-infected neurons in vivo and are the first to document and measure the rapid formation of TCEPs on these brain-infiltrating lymphocytes using live tissue imaging.

Original languageEnglish (US)
Pages (from-to)1823-1833
Number of pages11
JournalAmerican Journal of Pathology
Volume177
Issue number4
DOIs
StatePublished - Oct 2010

    Fingerprint

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this