The Role of CD8+ T Cells in Multiple Sclerosis and its Animal Models

The role of CD8+ T cells in multiple sclerosis (MS) and its animal models has been enigmatic. Most studies of MS have focused on the role of CD4+ Th1 T cells and many therapeutic strategies have been directed toward ameliorating the activity of this subset. Some of these strategies were effective in experimental autoimmune encephalomyelitis (EAE), a widely used animal model for MS dependent on CD4+ T cells, but paradoxically have worsened disease in MS patients. A great deal of evidence suggests that CD8+ T cells contribute to the pathogenesis of MS and should be considered in designing therapies. CD8+ T cells outnumber CD4+ T cells in MS lesions, and both clonal expansion and enrichment of memory cells is preferentially seen in the CD8+ T cell subset in the brain and cerebrospinal fluid of MS patients. New animal models have been developed that employ myelin-specific CD8+ T cells to induce central nervous system autoimmunity. In a CD8+ T cell model targeting myelin basic protein, clinical signs and pathology distinct from CD4+ T cell-mediated disease were observed that exhibited similarities to some aspects of MS. These differences are consistent with distinct effector mechanisms employed by CD8+ and CD4+ T cells in mediating tissue damage and suggest a need to consider the activity of CD8+ T cells in drug design. This review will focus on our current understanding of the role of CD8+ T cells in MS and the new animal models that allow us to investigate further the pathogenicity of this subset.