title: The CD8 T cell in multiple sclerosis: suppressor cell or mediator of neuropathology?
abstract: Multiple sclerosis (MS) is the most common human demyelinating disease of the central nervous system. It is universally accepted that the immune system plays a major role in the pathogenesis of MS. For decades, CD4 T cells have been considered the predominant mediator of neuropathology in MS. This perception was largely due to the similarity between MS and CD4 T-cell-driven experimental allergic encephalomyelitis, the most commonly studied murine model of MS. Over the last decade, several new observations in MS research imply an emerging role for CD8 T cells in neuropathogenesis. In certain experimental autoimmune encephalomyelitis (EAE) models, CD8 T cells are considered suppressors of pathology, whereas in other EAE models, neuropathology can be exacerbated by adoptive transfer of CD8 T cells. Studies using the Theiler's murine encephalomyelitis virus (TMEV) model have demonstrated preservation of motor function and axonal integrity in animals deficient in CD8 T cells or their effector molecules. CD8 T cells have also been demonstrated to be important regulators of blood-brain barrier permeability. There is also an emerging role for CD8 T cells in human MS. Human genetic studies reveal an important role for HLA class I molecules in MS susceptibility. In addition, neuropathologic studies demonstrate that CD8 T cells are the most numerous inflammatory infiltrate in MS lesions at all stages of lesion development. CD8 T cells are also capable of damaging neurons and axons in vitro. In this chapter, we discuss the neuropathologic, genetic, and experimental evidence for a critical role of CD8 T cells in the pathogenesis of MS and its most frequently studied animal models. We also highlight important new avenues for future research.
authors.affiliation: Department of Neurology, University of Cincinnati, Cincinnati, Ohio 45267, USA.
authors.forename: Aaron J
authors.initials: AJ
authors.lastname: Johnson
authors.forename: Georgette L
authors.initials: GL
authors.lastname: Suidan
authors.forename: Jeremiah
authors.initials: J
authors.lastname: McDole
authors.forename: Istvan
authors.initials: I
authors.lastname: Pirko
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology / Q000502:physiology*; D015234:HLA-A Antigens / Q000235:genetics / Q000378:metabolism; D015789:HLA-A2 Antigen; D006801:Humans; D008954:Models, Biological; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology*; D013601:T-Lymphocytes / Q000145:classification / Q000502:physiology; D050378:T-Lymphocytes, Regulatory / Q000473:pathology / Q000502:physiology
chemical_list: D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen