Resident T cells in the healthy and multiple sclerosis brain

Insights into T-cell biology in the central nervous system (CNS) have evolved from early neuroinflammatory models demonstrating the pathogenic potential of autoreactive T cells to recent human studies defining resident T-cell populations in the healthy and diseased brain. We here discuss advances in postmortem brain tissue processing, flow cytometry, and transcriptional profiling revealing that human brain CD8+ and CD4+ T cells are tissue-resident memory T cells with distinct phenotypes shaped by CNS borders and parenchymal niches. These findings refine our understanding of CNS immune surveillance and provide a framework for dissecting T-cell contributions to multiple sclerosis.