A Pathogenic Role for Myelin-Specific Cd8+ T Cells in a Model for Multiple Sclerosis

By E. Huseby, D. Liggitt, T. Brabb, Bryan Schnabel, Claes Öhlén, J. Goverman. Journal of Experimental Medicine, 2001

692 citations recorded by the source corpus.

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) characterized by plaques of infiltrating CD4+ and CD8+ T cells. Studies of MS and experimental autoimmune encephalomyelitis (EAE), an animal model of MS, focus on the contribution of CD4+ myelin-specific T cells. The role of CD8+ myelin-specific T cells in mediating EAE or MS has not been described previously. Here, we demonstrate that myelin-specific CD8+ T cells induce severe CNS autoimmunity in mice. The pathology and clinical symptoms in CD8+ T cell–mediated CNS autoimmunity demonstrate similarities to MS not seen in myelin-specific CD4+ T cell–mediated EAE. These data suggest that myelin-specific CD8+ T cells could function as effector cells in the pathogenesis of MS.

Subfields: Immunology, Pathology and Forensic Medicine

View Paper: https://www.semanticscholar.org/paper/41047c59dad6d13489ac30ec1819488a688204db

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Citations in the corpus

Immunology of multiple sclerosis. (2005, positive): “In the context of effector functions, however, CD8+ T cells are much better suited than CD4+ T cells to mediate CNS damage for the following reasons: (a) Except for microglia, none of the resident CNS cells express MHC class II; it can be induced on astrocytes by IFN-γ (32), but not on oligodendrocy”
Understanding pathogenesis and therapy of multiple sclerosis via animal models: 70 years of merits and culprits in experimental autoimmune encephalomyelitis research. (2006, background): “…T-cell-mediated inflammation AT-EAE in Lewis rat Ben-Nun et al. (1981) CD8+ T-cell-mediated inflammation Passive transfer of CD8+ T cells in mice Huseby et al. (2001), Cabarrocas et al. (2003), Sun et al. (2001) T-cell- and macrophage-mediated demyelination Chronic EAE in C57BL/6 mice induced…”
Three or more routes for leukocyte migration into the central nervous system (2003, result): “Recent results indicate that CD8 + T cells can mediate EAE and they are the main population that is clonally expanded in the brain of individuals with M”
New concepts in the immunopathogenesis of multiple sclerosis (2002, neutral): “Recently, myelin-specific CD8 + T CELLS were found to induce progressive EA”
Autoimmune T cell responses in the central nervous system (2009, background): “However, studies of myelin-specific CD8 + T cells showed that CD8 + T cells were highly pathogenic in EA”