T cell-targeted immunotherapies for multiple sclerosis: molecular mechanisms to therapeutic perspectives from...

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disorder of the central nervous system characterized by an imbalance between effector T cells (Th1/Th17) and regulatory T-cell (Treg) function. Current disease-modifying therapies (DMTs) reduce relapse frequency mainly through broad immunomodulation, but their non-specific mechanisms often lead to adverse effects and incomplete disease control, especially in progressive MS. These limitations have driven efforts to develop next-generation T-cell-targeted approaches, such as antigen-specific tolerance induction and adoptive Treg therapy. However, the highly oxidative inflammatory microenvironment within the central nervous system (CNS) of MS limits the development of these advanced T-cell-targeted therapies. Excessive reactive oxygen and nitrogen species (ROS/RNS) destabilize FoxP3 expression, interfere with IL-2 signaling, and promote Th17 differentiation, thereby reducing the stability and function of therapeutic T cells. This review summarizes the development of existing DMTs and emerging T-cell-targeted immunotherapies and reviews the current understanding of the underlying mechanisms. We further summarize evidence on bioactive compounds derived from Traditional Chinese Medicine (TCM) that can regulate ROS/RNS levels, reduce oxidative and inflammatory stress, and potentially serve as adjunct agents to improve the performance of cell-targeted therapies. In conclusion, we propose that future therapeutic strategies for MS may require the simultaneous targeting of autoreactive T-cell pathways and modulation of the CNS redox environment to maintain immune tolerance. Taken together, integrating T-cell immunotherapy with redox microenvironment modulation may enhance the durability of therapeutic responses and provide a conceptual rationale for combining TCM-based redox strategies with emerging cellular immunotherapies in the management of autoimmune neurological disorders.