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| Article Authors: | Jeremiah R McDole; Steve C Danzer; Raymund Y K Pun; Yi Chen; Holly L Johnson; Istvan Pirko; Aaron J Johnson |
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| Article Title: | Rapid formation of extended processes and engagement of Theiler's virus-infected neurons by CNS-infiltrating CD8 T cells. |
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| Reference ID: | 1020908 |
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| 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 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. |
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| Affiliations: | Departments of Neurology,University of Cincinnati College of Medicine , Cincinnati, OH 45267, USA. |
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| Date: | 2010 |
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| Reference Type: | Literature |
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| PubMed ID: | 20813972 |
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| Journal: | Am J Pathol |
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| Journal Volume: | 177 |
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| Article Pages: | 1823-33 |
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| Journal ISSN: | 1525-2191 |
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| Article Chemical List: | Epitopes, T-Lymphocyte |
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| Article MeSH List: | Adoptive Transfer; Animals; Brain(immunology; virology); CD8-Positive T-Lymphocytes(immunology; metabolism); Cardiovirus Infections(immunology; virology); Central Nervous System(immunology; virology); Central Nervous System Viral Diseases(immunology; virology); Epitopes, T-Lymphocyte(immunology); Female; Immunoenzyme Techniques; Lymphocyte Activation; Mice; Mice, Inbred C57BL; Neurons(immunology; virology); Theilovirus(immunology) |
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| Curation Last Updated: | 2011-08-24 00:46:23 |
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