Living rent free in your head: resident memory T cells

Tissue-resident memory T cells (TRM) are a distinct subset of memory T cells that persist long-term within non-lymphoid tissues and provide rapid, localized immune protection. The central nervous system (CNS) was among the first sites in which these TRM were detected, but only recently has their importance in brain immune surveillance been fully appreciated. Despite their relative low abundance, brain TRM can protect against reinfection, contribute to neuropathology, and participate in neurologic diseases. This review provides an overview of what is currently known about TRM in the brain, with a focus on CD8+ T cells, identifies major knowledge gaps, and highlights implications for human brain TRM biology. Addressing these gaps will help contextualize brain TRM in health and disease and guide strategies to harness or modulate them for vaccination and neuroimmune therapies.