T cell–neuron interaction in inflammatory and progressive multiple sclerosis biology

Multiple sclerosis (MS) is a chronic autoimmune condition of the central nervous system (CNS) characterized by acute inflammatory relapses, chronic neuro-axonal degeneration, and subsequent disability progression. T cells – in interaction with B cells and CNS-resident glial cells – are key initiators and drivers of neurodegeneration in MS. However, it is not entirely clear how encephalitogenic T cells orchestrate the local immune response within the brain and how they overtake disease stage-specific roles in MS pathogenesis. This review highlights recent advances in understanding direct and indirect T cell–neuron interactions in inflammatory and progressive MS. Finally, we discuss new diagnostic tools such as neurofilament light chain (NfL), which is on the cusp of becoming a key factor in clinical and therapeutic decision-making.