Targeting Inflammatory T Cells in Multiple Sclerosis: Current Therapies and Future Challenges

Abstract

Multiple Sclerosis (MS) is an autoimmune inflammatory disorder of the Central Nervous System (CNS), affecting more than one million people worldwide. The pathogenesis of MS involves several genetic and environmental factors, which ultimately lead to the activation of autoreactive T cells in the periphery, their migration into the CNS, where they trigger an acute inflammatory response, thus mediating primary demyelination and axonal damage. Most information on MS derives from studies in animal models of experimental autoimmune encephalomyelitis (EAE), which exhibit many similarities to the pathology of MS. Two distinct subsets of autoreactive T cells have been primarily involved in the pathogenesis of both EAE and MS: the interferon (IFN)-γ producing CD4+ T helper (Th) 1 and interleukin (IL)-17 producing Th17 cells. The activity of these cells is controlled by specific regulatory T cells (Treg), which by secreting anti-inflammatory cytokines such as IL-4, IL-10 and tumour growth factor (TGF)-β efficiently inhibit Th1 and Th17 cells. In this review, we summarize current knowledge on the role and function of pro-inflammatory and Treg subsets in MS. We also discuss the action of current and novel therapies aimed to dampen inflammatory T cells.