Figure 1.

Viral Infections Could Induce Bystander Generation of Pathogenic T Helper (Th)-1/17Cells. Local reactivations of neurotropic viruses in the central nervous system (CNS) parenchyma (A) leads to tissue damage and the uptake of both viral and myelin-derived antigens by dendritic cells (DCs). Virus-activated DCs then migrate via the cerebrospinal fluid (CSF) to draining deep cervical lymph nodes (B), present both viral and myelin-derived antigens to naïve and central memory T cells, and produce antiviral and proinflammatory cytokines, such as IL-12 and IL-1β. This not only leads to the priming of virus-specific Th1 cells, but could also result in the inappropriate stimulation of autoreactive CCR6⁺ T cells that are present in healthy individuals. Under the influence of IL-1β and/or IL-12, T cell receptor (TCR)-activated autoreactive CCR6⁺ central memory T cells (T_CM) could acquire CXCR3 expression and IFN-γ-producing capacities, and downregulate IL-10 production, thus differentiating into potentially encephalitogenic Th1/17_CM cells that are specifically expanded in patients with relapsing–remitting multiple sclerosis (RR-MS).