Abstract
Multiple sclerosis (MS) is a neurodegenerative disease resulting from an autoimmune attack on central nervous system (CNS) myelin. Although CD4+ T cell function in MS pathology has been extensively studied, there is also strong evidence that CD8+ T lymphocytes play a key role. Intriguingly, CD8+ T cells accumulate in great numbers in the CNS in progressive MS, a form of the disease that is refractory to current disease-modifying therapies that target the CD4+ T cell response. Here, we discuss the function of CD8+ T cells in experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. In particular, we describe EAE in non-obese diabetic (NOD) background mice, which develop a pattern of disease characterized by multiple attacks and remissions followed by a progressively worsening phase. This is highly reminiscent of the pattern of disease observed in nearly half of MS patients. Particular attention is paid to a newly described transgenic mouse strain (1C6) on the NOD background whose CD4+ and CD8+ T cells are directed against the encephalitogenic peptide MOG[35–55]. Use of this model will give us a more complete picture of the role(s) played by distinct T cell subsets in CNS autoimmunity.
Highlights
Multiple sclerosis (MS) is a complex chronic neurological disease that results from an immune-mediated attack against central nervous system (CNS) myelin
As epitopes 35–55 of myelin oligodendrocyte glycoprotein (MOG) are located in its extracellular domain, in the future it would be interesting to examine whether MHC class I-restricted peptides derived from myelin-associated glycoprotein (MAG) or proteolipid protein (PLP), both of which have extracellular domains (52), could induce CD8+ T cell-driven EAE
These findings suggest that MS and Type 1 diabetes (T1D) may share common pathogenic mechanisms
Summary
We describe EAE in non-obese diabetic (NOD) background mice, which develop a pattern of disease characterized by multiple attacks and remissions followed by a progressively worsening phase. Particular attention is paid to a newly described transgenic mouse strain (1C6) on the NOD background whose CD4+ and CD8+ T cells are directed against the encephalitogenic peptide MOG[35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55] Use of this model will give us a more complete picture of the role(s) played by distinct T cell subsets in CNS autoimmunity.
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