Rapid formation of extended processes and engagement of Theiler's virus-infected neurons by CNS-infiltrating CD8 T cells.
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 D(b):VP2(121-130). 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.
McDole
Jeremiah R
JR
Departments of Neurology,University of Cincinnati College of Medicine , Cincinnati, OH 45267, USA.
Danzer
Steve C
SC
Pun
Raymund Y K
RY
Chen
Yi
Y
Johnson
Holly L
HL
Pirko
Istvan
I
Johnson
Aaron J
AJ
D019264:Adoptive Transfer; D000818:Animals; D001921:Brain / Q000276:immunology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018188:Cardiovirus Infections / Q000276:immunology* / Q000821:virology; D002490:Central Nervous System / Q000276:immunology* / Q000821:virology; D020805:Central Nervous System Viral Diseases / Q000276:immunology* / Q000821:virology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D007124:Immunoenzyme Techniques; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000276:immunology* / Q000821:virology; D017945:Theilovirus / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte
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