The role of CD8 suppressors versus destructors in autoimmune central nervous system inflammation

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) of putative autoimmune origin. Recent evidence indicates that MS autoimmunity is linked to defects in regulatory T-cell function, which normally regulates immune responses to self-antigens and prevents autoimmune diseases. MS and its animal model, experimental autoimmune encephalomyelitis (EAE), have long been regarded as a CD4(+) T-cell-mediated autoimmune disease. Studies addressing the role of CD8(+) T cells, however, have only recently begun to emerge. Pathogenic function was attributed to CD8(+) T cells because of their abundant presence or oligoclonal repertoire within MS lesions. However, CD8(+) T cells appeared to have important regulatory functions, as demonstrated in EAE or human MS studies. We here review the contribution of CD8(+) T cells to inflammation and immune regulation in CNS autoimmunity. The knowledge of distinct CD8(+) T-cell populations exerting destructive versus beneficial functions is summarized. The long-term goal is to delineate the exact phenotypic and functional characteristics of regulatory CD8(+) T-cell populations (natural as well as inducible) in humans. This knowledge may help to further develop concepts of reconstituting or enhancing endogenous mechanisms of immune tolerance in future therapeutic concepts for MS.