The role of T cells in multiple sclerosis: implications for therapies targeting the T cell receptor.

The cause of multiple sclerosis (MS) is unknown, but an immunopathological process with both endogenous and exogenous factors contributing to disease seems likely. Considerable recent attention, triggered predominantly by findings in the animal model, experimental allergic encephalomyelitis (EAE), which resembles MS, has focused on the role of T cells in MS. Findings in the animal model have raised the possibility that demyelination could be produced by CD4+ T cells specific for myelin proteins and expressing a limited set of T cell receptor (TCR) molecules. Thus, specific therapies targeting T cells or more specifically the TCR could represent an effective treatment of MS as has been demonstrated in EAE. However, current studies of patients with MS indicate that the immunological mechanisms in MS are considerably more complicated than in EAE. The evidence for a pivotal role for T cells in MS and the characteristics of these T cells particularly with respect to TCR usage and potential for therapies directed at the TCR will be examined in this review.