Abstract
Brain atrophy is a common feature of numerous neurologic diseases in which the role of neuroinflammation remains ill-defined. In this study, we evaluated the contribution ofmajor histocompatibility complex class I molecules to brain atrophy in Theiler's murine encephalomyelitis virus (TMEV)-infected transgenic FVB mice that express the Db class I molecule. FVB/Db and wild-type FVB mice were evaluated for changes in neuroinflammation, virus clearance, neuropathology, and development of brain atrophy via T2-weighted MRI and subsequent 3-dimensional volumetric analysis. Significant brain atrophy and hippocampal neuronal loss were observed in TMEV-infected FVB/Db mice, but not in wild-type FVB mice. Brain atrophy was observed at 1 mo postinfection and persisted through the 4-mo observation period. Of importance, virus-infected FVB/Db mice elicited a strongCD8T-cell response towardthe immunodominantDb-restrictedTMEV-derived peptide, VP2121-130, and cleared TMEV from the CNS. In addition, immunofluorescence revealed CD8 T cells near virus-infected neurons; therefore, we hypothesize that class I restricted CD8 T-cell responses promote development of brain atrophy. This model provides an opportunity to analyze the contribution of immune cells to brain atrophy in a system where persistent virus infection and demyelination are not factors in long-term neuropathology.
Original language | English (US) |
---|---|
Pages (from-to) | 2267-2275 |
Number of pages | 9 |
Journal | FASEB Journal |
Volume | 31 |
Issue number | 6 |
DOIs | |
State | Published - Jun 2017 |
Keywords
- CD8 T cells
- MHC class I
- Neurodegeneration
- TMEV
- Viral clearance
ASJC Scopus subject areas
- Biotechnology
- Biochemistry
- Molecular Biology
- Genetics