Departments of Medicine.
Pathology and Immunology.
Curr Opin Neurol. 2020 Jun;33(3):405-412. doi: 10.1097/WCO.0000000000000825.
The present review will outline neuroprotective and neurotoxic effects of central nervous system (CNS) infiltrating T cells during viral infections. Evidence demonstrating differential roles for antiviral effector and resident memory T-cell subsets in virologic control and immunopathology in the CNS will be discussed. Potential therapeutic targets emanating from a growing understanding of T-cell-initiated neuropathology that impacts learning and memory will also be delineated.
The critical role for T cells in preventing and clearing CNS infections became incontrovertible during the era of acquired immunodeficiency syndrome. Recent studies have further defined differential roles of T-cell subsets, including resident memory T cells (Trm), in antiviral immunity and, unexpectedly, in postinfectious cognitive dysfunction. Mechanisms of T-cell-mediated effects include differential innate immune signaling within neural cells that are virus-specific.
T-cell cytokines that are essential for cell-mediated virologic control during neurotropic viral infections have recently been identified as potential targets to prevent post-infection memory disorders. Further identification of T-cell subsets, their antigen specificity, and postinfection localization of Trm will enhance the efficacy of immunotherapies through minimization of immunopathology.
本综述将概述中枢神经系统(CNS)浸润性 T 细胞在病毒感染期间的神经保护和神经毒性作用。将讨论证据表明抗病毒效应和驻留记忆 T 细胞亚群在 CNS 病毒学控制和免疫病理学中的不同作用。还将阐述从日益增长的对影响学习和记忆的 T 细胞引发的神经病理学的理解中产生的潜在治疗靶点。
在获得性免疫缺陷综合征时代,T 细胞在预防和清除中枢神经系统感染方面的关键作用已不容置疑。最近的研究进一步确定了 T 细胞亚群的不同作用,包括驻留记忆 T 细胞(Trm),在抗病毒免疫中,以及出乎意料的是,在感染后认知功能障碍中的作用。T 细胞介导的作用机制包括病毒特异性神经细胞内差异的先天免疫信号传导。
在神经嗜性病毒感染期间,细胞介导的病毒学控制所必需的 T 细胞细胞因子最近被确定为预防感染后记忆障碍的潜在靶点。进一步鉴定 T 细胞亚群、其抗原特异性以及 Trm 的感染后定位将通过最小化免疫病理学来提高免疫疗法的疗效。