The role of T cells and the innate immune system in the pathogenesis of theiler's virus demyeliating disease

The immune response to TMEV involves activation of both the innate and adaptive immune responses. The innate immune response is the initial response by the host to a viral infection. The adaptive immune response follows the initial response and is mediated by CD8⁺ and CD4⁺ T cell and antibody responses specific to the viral antigens. CNS pathogenesis in TMEV-IDD is associated with long-term virus persistence in CNS-resident microglia and macrophages which leads to the activation of a virus-specific CD4⁺ Th1 response. Myelin destruction is initiated by the bystander effector functions of CNS-resident mononuclear cells which are activated both directly by the innate immune response to persistent TMEV infection and indirectly by pro-inflammatory cytokines released by virus-specific Th1 cells. Initial myelin destruction leads to the release of myelin antigens and the subsequent activation of myelin epitope-specific autoreactive CD4⁺ Th1 cells via epitope spreading which are largely responsible for chronic disease progression.