Multiple sclerosis (MS) is a T cell driven autoimmune disease of the central nervous system (CNS). Despite its association with Epstein-Barr Virus (EBV), how viral infections promote MS remains unclear. However, there is increasing evidence that the CNS is continuously surveyed by virus-specific T cells, which protect against reactivating neurotropic viruses. Here, we discuss how viral infections could lead to the breakdown of self-tolerance in genetically predisposed individuals, and how the reactivations of viruses in the CNS could induce the recruitment of both autoaggressive and virus-specific T cell subsets, causing relapses and progressive disability. A disturbed immune surveillance in MS would explain several experimental findings, and has important implications for prognosis and therapy. A huge body of evidence suggests that viral infections promote MS; however, no single causal virus has been identified. Multiple viruses could promote MS via bystander effects.Molecular mimicry is an established pathogenic mechanism in selected autoimmune diseases. It is also well documented in MS, but its contribution to MS pathogenesis is still unclear.Bystander activation upon viral infection could be involved in the generation of the autoreactive and potentially encephalitogenic T helper (Th)-1/17 central memory (Th1/17CM) cells found in the circulation of patients with MS.Autoreactive Th1/17CM cells could expand at the cost of antiviral Th1CM cells in patients with MS, in particular in those undergoing natalizumab therapy, because these cells are expected to compete for the same homeostatic niche.Autoreactive Th1/17 cells and antiviral Th1 cells are recruited to the CSF of patients with MS following attacks, suggesting that viral reactivations in the CNS induce the recruitment of pathogenic Th1/17 cells. Autoreactive Th1/17 cells in the CNS might also induce de novo viral reactivations in a circuit of self-induced inflammation.
ASJC Scopus subject areas
- Immunology and Allergy