Beyond the blood-brain barrier: unraveling T cell subsets in CNS immunity and disease

The complicated interplay between the central nervous system (CNS) and immune system is critical for both neuroprotection and neurodegeneration. T lymphocytes are key players in CNS immunity, with distinct subgroups that work in a highly dynamic and, sometimes, antagonistic manner depending on the disorder. This review covers T-cell subgroups with a focus on pathogenic Th1 and Th17 cells and their role in mediating neuronal death and demyelination in multiple sclerosis (MS) and stroke, as well as the neurotoxic nature of CD8+ cytotoxic T lymphocytes and the neuroprotective and immunosuppressive roles of regulatory T cells (Tregs) that promote CNS homeostasis. In answer to the overwhelming need for effective pharmacotherapy, we overview of available pharmacotherapies that have the potential to target the aforementioned T-cell subsets. Treatments ultimately include broad-spectrum immunosuppressants, highly specific monoclonal antibodies, and new small-molecule inhibitors. Clinical data are added whenever possible to assess how these therapies interact with T-cell activity to restore immune balance in the CNS. This review highlights the evolution of treatment progress and the growing paradigm shift towards precision medicine through the targeting of T-cell subsets in neuroinflammatory diseases.