T cells in multiple sclerosis

Inflammatory demyelination and axonal damage in the central nervous system (CNS) are hallmarks of multiple sclerosis (MS). The overwhelming number of susceptibility variants in genome wide association studies affects genes with immune functions, suggesting that the initiation of the disease is caused by dysregulated immune responses. In this chapter, I will review the arguments that speak in favor of autoreactive T cells as initiators and major orchestrators of inflammatory episodes in the CNS. Concepts of T cell activation in the systemic immune compartment by mimotopes of autoantigens or in CNS draining lymph nodes by true autoantigens will be discussed as well as the routes of infiltration and the sites of reactivation of T cells in the CNS. More recent findings on tissue imprinting of T cells that invade the CNS and on tissue resident memory T cells will be summarized as to their significance for CNS autoimmunity. Finally, I will point out which features of MS are likely no longer dependent on CNS invading T cells. Together, this chapter will give an overview over the functional phenotypes of T cells in the systemic immune compartment, the cerebrospinal fluid and the CNS parenchyma in MS and integrate these findings into a comprehensive pathogenic concept of T cell driven autoimmunity in the CNS.