Multiple sclerosis (MS) is an inflammatory, demyelinating, and neurodegenerative disorder of the CNS. The etiology of MS remains unknown. However, it is well established that immune dysregulation plays a critical role in the neuropathogenesis of this disorder. In this review, we discuss the current hypotheses concerning the complex cellular and molecular interactions involved in the immunopathogenesis of MS. Although CD4+ T lymphocytes have long been considered the critical cellular factor in the immunopathology of MS, the role of other cell types has also recently been investigated. It appears that the spatial distribution of CD4+ and CD8+ cells in MS lesions is distinct. Yet another T-lymphocyte subset, γ/δ T cells, can be detected in very early MS lesions. The prevalent dogma suggests that CD4+ helper T (TH) type 1 cells release cytokines and inflammatory mediators that cause tissue damage, while CD4+ TH2 cells might be involved in modulation of these effects. However, a mounting body of evidence suggests that additional T-cell subsets, including TH17 cells, CD8+ effector T cells, and CD4+ CD25+ regulatory T cells, also affect disease activity. In addition, clinical and paraclinical data are accumulating on the prominent role of B lymphocytes and other antigen-presenting cells in MS neuropathogenesis. Given these observations, new therapeutic interventions for MS will need to focus on resetting multiple components of the immune system
Relationship Disclosure: Dr Awad has nothing to disclose. Dr Stüve has received personal compensation for speaking engagements from Teva Neuroscience and in an editorial capacity from Archives of Neurology. Dr Stüve's compensation and/or research work has been funded, entirely or in part, by a grant to his university from a governmental organization and a for-profit organization. The grant agreement requires that the name of the funding entity and the purpose of the grant may not be disclosed.
Unlabeled Use of Products/Investigational Use Disclosure: Dr Awad discusses investigational drugs and modalities such as stem cell transplant, alemtuzumab, cladribine, rituximab, daclizumab, fingolimod, laquinimod, teriflunomide, and BG00012. Dr Stüve has nothing to disclose.