T cell-mediated immunodysregulation in multiple sclerosis: from pathogenic subsets to therapeutic advances

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) caused by chronic inflammation. It is the leading cause of neurologic symptoms in young people and leads to progressive neurodegenerative disability. Accumulating evidence indicates that MS arises from the coordinated and co-dominant actions of peripheral immune cells, meningeal tertiary lymphoid structures (TLS), and CNS-resident immune compartments. Within this complex immunopathological network, dysregulated T-cell-mediated adaptive immune responses play a pivotal role in initiating and organizing autoimmune inflammation. Peripherally activated T cells cross the blood-brain barrier (BBB), become reactivated within the CNS, and secrete pro-inflammatory cytokines that drive demyelination and neurodegeneration. Improved understanding of these immune mechanisms has led to the development of disease-modifying therapies (DMTs), many of which directly or indirectly target T-cell function. Here, we adopt a T-cell-centric perspective to systematically review the pathogenic mechanisms of MS, with particular emphasis on recent advances and unresolved questions regarding T-cell subset dysregulation, systematically integrating its precise targeting associations with conventional disease-modifying therapies (DMTs). Simultaneously, the mechanisms of emerging therapies were analyzed, and the potential of traditional herbal medicines was explored. This approach overcomes the limitations of previous studies that focused solely on a single T cell subset or a single therapeutic category.