Abstract |
Theiler's murine encephalomyelitis (TME) of susceptible mouse strains is a commonly used infectious animal model for multiple sclerosis. The study aim was to test the hypothesis whether cytotoxic T cell responses account for the limited impact of regulatory T cells on antiviral immunity in TME virus-induced demyelinating disease (TMEV-IDD) resistant C57BL/6 mice. TME virus-infected C57BL/6 mice were treated with (i) interleukin-2/-anti- interleukin-2-antibody-complexes to expand regulatory T cells ("Treg-expansion"), (ii) anti-CD8-antibodies to deplete cytotoxic T cells ("CD8-depletion") or (iii) with a combination of Treg-expansion and CD8-depletion ("combined treatment") prior to infection. Results showed that "combined treatment", but neither sole "Treg-expansion" nor "CD8-depletion," leads to sustained hippocampal infection and virus spread to the spinal cord in C57BL/6 mice. Prolonged infection reduces myelin basic protein expression in the spinal cord together with increased accumulation of β- amyloid precursor protein in axons, characteristic of myelin loss and axonal damage, respectively. Chronic spinal cord infection upon "combined treatment" was also associated with increased T and B cell recruitment, accumulation of CD107b+ microglia/macrophages and enhanced mRNA expression of interleukin (IL)-1α, IL-10 and tumor necrosis factor α. In conclusion, data revealed that the suppressive capacity of Treg on viral elimination is efficiently boosted by CD8-depletion, which renders C57BL/6 mice susceptible to develop chronic neuroinfection and TMEV-IDD.
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Authors | Malgorzata Ciurkiewicz, Vanessa Herder, Muhammad Akram Khan, Ann-Kathrin Uhde, René Teich, Stephan Floess, Wolfgang Baumgärtner, Jochen Huehn, Andreas Beineke |
Journal | Brain pathology (Zurich, Switzerland)
(Brain Pathol)
Vol. 28
Issue 3
Pg. 349-368
(05 2018)
ISSN: 1750-3639 [Electronic] Switzerland |
PMID | 28452087
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2017 International Society of Neuropathology. |
Topics |
- Animals
- Brain
(immunology, virology)
- CD8-Positive T-Lymphocytes
(immunology)
- Cardiovirus Infections
(immunology)
- Demyelinating Diseases
(immunology, virology)
- Disease Models, Animal
- Female
- Mice, Inbred C57BL
- Spinal Cord
(immunology, virology)
- T-Lymphocytes, Regulatory
(immunology)
- Theilovirus
(immunology)
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