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.
Goverman
Joan
J
Department of Immunology, University of Washington, Box 357650, Seattle, WA 98195, USA. goverman@u.washington.edu
Perchellet
Antoine
A
Huseby
Eric S
ES
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D002490:Central Nervous System / Q000166:cytology / Q000276:immunology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology; D006801:Humans; D009103:Multiple Sclerosis / Q000503:physiopathology* / Q000821:virology