CD8-mediated inflammatory central nervous system disorders

Abstract

In central nervous system (CNS) autoimmune disorders, CD8+ T cells have been reported to exert cytotoxic as well as regulatory functions. In virus-induced (meningo) encephalitis, they are essential for viral clearance, but can also cause severe immunopathology. This review aims to summarize the multifaceted roles CD8+ T cells can play in inflammatory CNS disorders. Recent evidence for a role of CD8+ T cells in multiple sclerosis comes from genetic association studies confirming a protective effect of the HLA-A0201 allele. Besides their dominance in white matter lesions, CD8+ T cells contribute to immune infiltrates in cortical demyelinating lesions. Having infiltrated the CNS, CD8+ T cells migrate along an inflammation-induced fibrous network. Although CD8+ T cells are generally considered to be crucial for acute viral clearance, they can also induce autoimmune-like immunopathology by, for example, encountering a virus in adulthood while being at the same time latently infected by a related virus. Inadequate control of latent viruses under immunosuppressive treatments or immunodeficiencies is becoming increasingly important in neurology clinical work. Future research should aim at identifying the specificity and functional phenotype of brain-infiltrating CD8+ T cells in autoimmune diseases and viral immunopathology in order to develop therapeutic strategies specifically targeting CNS-relevant immune reactions.