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

Author(s): Joan Goverman, Antoine Perchellet, Eric S. Huseby.

Journal Name: Current Drug Targets - Inflammation & Allergy

Volume 4 , Issue 2 , 2005

Abstract:

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.

Keywords: inflammatory disease, central nervous system (cns), demyelination, experimental autoimmune encephalomyelitis (eae), myelin-associated glycoprotein (mag), lymphocyte, viral infections, cytotoxic t lymphocyte (ctl)

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Article Details

VOLUME: 4
ISSUE: 2
Year: 2005
Page: [239 - 245]
Pages: 7
DOI: 10.2174/1568010053586264
Price: $58

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