Cytotoxic CD8+ T cells ablation enhances the capacity of regulatory T cells to delay viral elimination in Theiler's murine encephalomyelitis

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. Chronic spinal cord infection upon 'combined treatment' mice 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. 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. This article is protected by copyright. All rights reserved.

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