The central nervous system (CNS) is classically viewed as immune-privileged; however, recent advances highlight interactions between the peripheral immune system and CNS in controlling infections and tissue homeostasis. Tissue-resident memory (T_RM) CD8⁺ T cells in the CNS are generated after brain infections, but it is unknown whether CNS infection is required to generate brain T_RM cells. We show that peripheral infections generate antigen-specific CD8⁺ memory T cells in the brain that adopt a unique T_RM signature. Upon depletion of circulating and perivascular memory T cells, this brain signature was enriched and the surveilling properties of brain T_RM cells was revealed by intravital imaging. Notably, peripherally induced brain T_RM cells showed evidence of rapid activation and enhanced cytokine production and mediated protection after brain infections. These data reveal that peripheral immunizations can generate brain T_RM cells and will guide potential use of T cells as therapeutic strategies against CNS infections and neurological diseases.

中枢神经系统 (CNS) 传统上被认为具有免疫特权。然而，最近的进展强调了外周免疫系统和中枢神经系统在控制感染和组织稳态方面的相互作用。脑部感染后会产生中枢神经系统中的组织驻留记忆（ _TRM ）CD8 ⁺ T细胞，但尚不清楚中枢神经系统感染是否需要产生脑部_TRM细胞。我们发现，外周感染会在大脑中产生抗原特异性 CD8 ⁺记忆 T 细胞，这些细胞采用独特的 T _RM特征。当循环和血管周围记忆 T 细胞耗尽后，这种大脑特征就会丰富，并且通过活体成像揭示了大脑 T _RM细胞的监视特性。值得注意的是，外周诱导的脑 T _RM细胞显示出快速激活、细胞因子产生增强以及脑感染后介导的保护的证据。这些数据表明，外周免疫可以产生脑 T _RM细胞，并将指导 T 细胞作为针对中枢神经系统感染和神经系统疾病的治疗策略的潜在用途。