The Non-Obese Diabetic Mouse Strain as a Model to Study CD8+ T Cell Function in Relapsing and Progressive Multiple Sclerosis

Prenitha Mercy Ignatius Arokia Doss, Andrée-Pascale Roy, AiLi Wang, Ana Carrizosa Anderson, Manu Rangachari

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.