Specificity of Adaptive Immune Responses in Central Nervous System Health, Aging and Diseases

The field of neuroimmunology endorses the involvement of the adaptive immune system in central nervous system (CNS) health, disease, and aging. While immune cell trafficking into the CNS is highly regulated, small numbers of antigen-experienced lymphocytes can still enter the cerebrospinal fluid (CSF)-filled compartments for regular immune surveillance under homeostatic conditions. Meningeal lymphatics facilitate drainage of brain-derived antigens from the CSF to deep cervical lymph nodes to prime potential adaptive immune responses. During aging and CNS disorders, brain barriers and meningeal lymphatic functions are impaired, and immune cell trafficking and antigen efflux are altered. In this context, alterations in the immune cell repertoire of blood and CSF and T and B cells primed against CNS-derived autoantigens have been observed in various CNS disorders. However, for many diseases, a causal relationship between observed immune responses and neuropathological findings is lacking. Here, we review recent discoveries about the association between the adaptive immune system and CNS disorders such as autoimmune neuroinflammatory and neurodegenerative diseases. We focus on the current challenges in identifying specific T cell epitopes in CNS diseases and discuss the potential implications for future diagnostic and treatment options.