CD8⁺ T cells in viral encephalitis: context-dependent control of antiviral immunity and neuroinflammation

Viral encephalitis is a severe neuroinflammatory condition resulting from neurotropic viral invasion of the central nervous system (CNS), characterized by long-term neurological sequelae and high mortality. Accumulating evidence indicates that immune responses mediated by CD8 + T cells play a vital role in shaping disease outcomes. However, the specific mechanisms underlying the roles of CD8⁺ T cells in viral encephalitis remain poorly understood. Given that infiltrating CD8 + T cells may lead to excessive inflammation if not precisely regulated, this review synthesizes the current evidence to highlight how the microenvironment, disease stage, and host status determine whether CD8⁺ T cell responses are protective or pathogenic in viral encephalitis. Furthermore, we summarize potential therapeutic targets involving CD8 + T cells. Additionally, we provide an overview of the major routes of CNS invasion by neurotropic viruses and the subsequent initiation of antiviral immune responses. Elucidating the heterogeneous roles of CD8⁺ T cells in different types of viral encephalitis may help identify novel therapeutic targets for personalized immunotherapy in patients with viral encephalitis.