Cytotoxic <scp>CD</scp>8⁺<scp>T</scp> cell ablation enhances the capacity of regulatory T cells to delay viral elimination in <scp>T</scp>heiler's murine encephalomyelitis

Abstract

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.