The role of regulatory T cells in multiple sclerosis

Regulatory T (TREG) cells are emerging as key players in the pathogenetic scenario of CNS autoimmune inflammation. In this article, Zozulya and Wiendl discuss how TREG-cell dysfunction might influence the disease course in multiple sclerosis and experimental autoimmune encephalomyelitis, highlighting the importance of interactions between TREGcells and dendritic cells. The authors also assess the potential for therapeutic use of these cell types in patients with multiple sclerosis. The dysregulation of inflammatory responses and of immune self-tolerance is considered to be a key element in the autoreactive immune response in multiple sclerosis (MS). Regulatory T (TREG) cells have emerged as crucial players in the pathogenetic scenario of CNS autoimmune inflammation. Targeted deletion of TREG cells causes spontaneous autoimmune disease in mice, whereas augmentation of TREG-cell function can prevent the development of or alleviate variants of experimental autoimmune encephalomyelitis, the animal model of MS. Recent findings indicate that MS itself is also accompanied by dysfunction or impaired maturation of TREG cells. The development and function of TREG cells is closely linked to dendritic cells (DCs), which have a central role in the activation and reactivation of encephalitogenic cells in the CNS. DCs and TREG cells have an intimate bidirectional relationship, and, in combination with other factors and cell types, certain types of DCs are capable of inducing TREG cells. Consequently, TREG cells and DCs have been recognized as potential therapeutic targets in MS. This Review compiles the current knowledge on the role and function of various subsets of TREG cells in MS and experimental autoimmune encephalomyelitis. We also highlight the role of tolerogenic DCs and their bidirectional interaction with TREG cells during CNS autoimmunity.