Department of Medicine, Section of General Pathology, University of Verona, Verona, Italy.
Front Immunol. 2023 Jul 28;14:1233870. doi: 10.3389/fimmu.2023.1233870. eCollection 2023.
CD8+ lymphocytes are adaptive immunity cells with the particular function to directly kill the target cell following antigen recognition in the context of MHC class I. In addition, CD8+ T cells may release pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), and a plethora of other cytokines and chemoattractants modulating immune and inflammatory responses. A role for CD8+ T cells has been suggested in aging and several diseases of the central nervous system (CNS), including Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, limbic encephalitis-induced temporal lobe epilepsy and Susac syndrome. Here we discuss the phenotypic and functional alterations of CD8+ T cell compartment during these conditions, highlighting similarities and differences between CNS disorders. Particularly, we describe the pathological changes in CD8+ T cell memory phenotypes emphasizing the role of senescence and exhaustion in promoting neuroinflammation and neurodegeneration. We also discuss the relevance of trafficking molecules such as selectins, mucins and integrins controlling the extravasation of CD8+ T cells into the CNS and promoting disease development. Finally, we discuss how CD8+ T cells may induce CNS tissue damage leading to neurodegeneration and suggest that targeting detrimental CD8+ T cells functions may have therapeutic effect in CNS disorders.
CD8+ 淋巴细胞是适应性免疫细胞，具有在 MHC Ⅰ 类分子背景下识别抗原后直接杀死靶细胞的特殊功能。此外，CD8+T 细胞可能释放促炎细胞因子，如肿瘤坏死因子-α（TNF-α）和干扰素-γ（IFN-γ），以及大量其他细胞因子和趋化因子，调节免疫和炎症反应。CD8+T 细胞在衰老和中枢神经系统（CNS）的几种疾病中发挥作用，包括阿尔茨海默病、帕金森病、多发性硬化症、肌萎缩侧索硬化症、边缘性脑炎引起的颞叶癫痫和 Susac 综合征。在这里，我们讨论了这些情况下 CD8+T 细胞区室的表型和功能改变，强调了中枢神经系统疾病之间的相似性和差异。特别是，我们描述了 CD8+T 细胞记忆表型的病理变化，强调衰老和衰竭在促进神经炎症和神经退行性变中的作用。我们还讨论了选择素、粘蛋白和整合素等运输分子在控制 CD8+T 细胞进入中枢神经系统和促进疾病发展中的相关性。最后，我们讨论了 CD8+T 细胞如何诱导中枢神经系统组织损伤导致神经退行性变，并提出靶向有害 CD8+T 细胞功能可能对中枢神经系统疾病具有治疗作用。
