Role of CD4(+) T Cells in the Pathophysiology of Multiple Sclerosis

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. Although the precise etiology of MS remains unclear, CD4(+) T cells have been proposed to play not only effector but also regulatory roles in MS. CD4(+) T cells can be divided into four subsets: pro-inflammatory helper T (Th) 1 and Th17 cells, anti-inflammatory Th2 cells and regulatory T cells (Tregs). The roles of CD4(+) T cells in MS have been clarified by either “loss-of-function” or “gain-of-function” methods, which have been carried out mainly in autoimmune and viral models of MS: experimental autoimmune encephalomyelitis and Theiler's murine encephalomyelitis virus infection, respectively. Observations in MS patients were consistent with the mechanisms found in the MS models, that is, increased pro-inflammatory Th1 and Th17 activity is associated with disease exacerbation, while anti-inflammatory Th2 cells and Tregs appear to play a protective role.