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 immunopatholog ical process with both endogenous and exogenous factors contributing t o disease seems likely. Considerable recent attention, triggered predo minantly by findings in the animal model, experimental allergic enceph alomyelitis (EAE), which resembles MS, has focused on the role of T ce lls in MS. Findings in the animal model have raised the possibility th at demyelination could be produced by CD4+ T cells specific for myelin proteins and expressing a limited set of T cell receptor (TCR) molecu les. Thus, specific therapies targeting T cells or more specifically t he TCR could represent an effective treatment of MS as has been demons trated in EAE. However, current studies of patients with MS indicate t hat the immunological mechanisms in MS are considerably more complicat ed 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.