Virus-induced CD8 + T cells accelerate the onset of experimental autoimmune encephalomyelitis: Implications for how viral infections might trigger multiple sclerosis exacerbations

• Asymptomatic Sindbis virus encephalomyelitis transiently accelerates EAE symptoms.
• Infection does not alter expansion or differentiation of autoreactive CD4 + T cells.
• Virus-induced CD8 + T cells drive this effect on the clinical course of EAE.

Viral infections can exacerbate multiple sclerosis (MS) through poorly defined mechanisms. We developed an experimental system whereby infection with an asymptomatic neurotropic alphavirus caused a transient acceleration of experimental autoimmune encephalomyelitis (EAE) without altering the expansion or differentiation of autoreactive CD4 + T cells. Instead, this effect on the clinical course of EAE depended on CD8 + T cells that neither participate in viral clearance nor induce neuropathology in infected mice without EAE. Our system should be useful to further unravel how certain viral infections trigger MS exacerbations and to understand how CD8 + T cells can exert pathogenic effects within active demyelinating lesions.