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An Ex vivo Model of an Oligodendrocyte-directed T-Cell Attack in Acute Brain Slices
Published on: February 5, 2015
Apoptotic cells, including macrophages, are prominent in Theiler's virus-induced inflammatory, demyelinating lesions
Brian P Schlitt1, Matthew Felrice, Mary Lou Jelachich
1Department of Neurology, Northwestern University, Evanston, Illinois, USA.
Abstract:
Theiler's murine encephalomyelitis virus (TMEV) persists in the mouse central nervous system principally in macrophages, and infected macrophages in culture undergo apoptosis. We have detected abundant apoptotic cells in perivascular cuffs and inflammatory, demyelinating lesions of SJL mice chronically infected with TMEV. T cells comprised 74% of apoptotic cells, while 8% were macrophages, 0.6% were astrocytes, and approximately 17% remained unidentified. In situ hybridization revealed viral RNA in approximately 1% of apoptotic cells.
Insights
Theiler's murine encephalomyelitis virus (TMEV) causes apoptosis in the mouse central nervous system, primarily affecting T cells within inflammatory lesions. Viral RNA was detected in a small fraction of these apoptotic cells.
Area of Science:
- Neurovirology
- Immunology
- Pathology
Background:
- Theiler's murine encephalomyelitis virus (TMEV) establishes persistent infections in the mouse central nervous system (CNS).
- Macrophages are the primary cell type harboring TMEV in the CNS, and TMEV-infected macrophages exhibit apoptosis in vitro.
- Apoptotic cells are observed in the CNS during chronic TMEV infection.
Purpose of the Study:
- To investigate the cellular composition of apoptotic cells within the CNS of TMEV-infected mice.
- To determine the presence of viral RNA in apoptotic cells during chronic TMEV infection.
Main Methods:
- Histological examination of CNS lesions from chronically TMEV-infected SJL mice.
- Identification of apoptotic cells using morphological criteria.
- Cellular typing of apoptotic cells (T cells, macrophages, astrocytes).
- In situ hybridization to detect viral RNA within apoptotic cells.
Main Results:
- Abundant apoptotic cells were found in perivascular cuffs and inflammatory, demyelinating lesions.
- T cells constituted the majority (74%) of apoptotic cells, followed by macrophages (8%) and astrocytes (0.6%).
- Viral RNA was detected in approximately 1% of the identified apoptotic cells.
Conclusions:
- T cells are significantly involved in apoptosis within the CNS during chronic TMEV infection.
- While macrophages harbor the virus, T cells are the predominant apoptotic cell type in lesions.
- The low percentage of viral RNA in apoptotic cells suggests complex mechanisms of cell death and viral persistence.
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