Activation and Long-Term Maintenance of Adaptive Immunity in the Central Nervous System: A Double-Edged Sword?

Abstract

Background: For a long time, the brain was considered an organ with “immune privilege”, where microglial cells played a phagocytic role, maintaining immune self-sufficiency. However, recent studies have revealed the presence of immune-related structures and immune cell infiltration in the brain, which participates in adaptive immunity. Aim of Review: This review aims to synthesize recent findings on the activation and long-term maintenance of adaptive immunity in the central nervous system (CNS), exploring how adaptive immune responses function in pathogen clearance, tumor defense, and CNS inflammation. It highlights both the protective and detrimental roles of adaptive immunity in these contexts. Key Scientific Concepts: Antigen-presenting cells (APCs) present antigen information to naive T cells, initiating adaptive immunity in the CNS. Activated T cells can differentiate into effector T cells to perform immediate immune functions or into tissue-resident memory T cells (TRMs) that persist in the CNS, providing long-term immune surveillance. Over the past 15 years, studies have shown that adaptive immunity is activated and maintained during intracranial pathogen infections, brain tumors, and CNS inflammation. While adaptive immunity can clear pathogens, eliminate tumor cells, and protect the brain, it can also lead to CNS inflammation under certain conditions, resulting in undesirable outcomes.