Le Page Aurélie, Bourgade Karine, Lamoureux Julie, Frost Eric, Pawelec Graham, Larbi Anis, Witkowski Jacek M, Dupuis Gilles, Fülöp Tamás
Research Center on Aging, Graduate Program in Immunology, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, QC, Canada.
Graduate Program in Physiology-Biophysics, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, Sherbrooke, QC, Canada.
J Alzheimers Dis. 2015;46(1):93-107. doi: 10.3233/JAD-143054.
Alzheimerś disease (AD) is a progressive irreversible neurological brain disorder characterized by accumulation of amyloid-β, amyloid plaques, and neurofibrillary tangles. Inflammation and immune alterations have been linked to AD, suggesting that the peripheral immune system plays a role during the asymptomatic period of AD. NK cells participate in innate immune surveillance against intracellular pathogens and malignancy but their role in AD remains controversial. We have investigated changes in peripheral NK cell phenotypes and functions in amnestic mild cognitive impairment (aMCI, n = 10), patients with mild AD (mAD, n = 11), and healthy elderly controls (n = 10). Patients selected according to NINCDS-ADRDA criteria were classified using neuropsychological assessment tests. Phenotype analysis revealed differences in expression of CD16 (increased in mAD), NKG2A (decreased in aMCI), and TLR2 and TLR9 (both decreased in mAD). Functional assays revealed that NK cell killing activity and degranulation (CD107 expression) were unchanged in the three groups. In contrast, expression of the CD95 receptor was increased in aMCI and mAD. Granzyme B expression and cytokine production (TNFα, IFNγ) were increased in aMCI but not in mAD. CCL19- but not CCL21-dependent chemotaxis was decreased in aMCI and mAD, despite the fact that CCR7 expression was increased in aMCI. Our data suggest that the number of alterations observed in peripheral NK cells in aMCI represent an activation state compared to mAD patients and that may reflect an active immune response against a still to be defined aggression.
阿尔茨海默病（AD）是一种进行性不可逆的神经脑部疾病，其特征为β淀粉样蛋白、淀粉样斑块和神经原纤维缠结的积累。炎症和免疫改变与AD有关，这表明外周免疫系统在AD的无症状期发挥作用。自然杀伤细胞（NK细胞）参与针对细胞内病原体和恶性肿瘤的先天性免疫监视，但其在AD中的作用仍存在争议。我们研究了遗忘型轻度认知障碍（aMCI，n = 10）、轻度AD患者（mAD，n = 11）和健康老年对照（n = 10）外周NK细胞表型和功能的变化。根据NINCDS-ADRDA标准选择的患者使用神经心理学评估测试进行分类。表型分析显示，CD16的表达存在差异（mAD中增加）、NKG2A（aMCI中降低）以及TLR2和TLR9（两者在mAD中均降低）。功能测定显示，三组中NK细胞的杀伤活性和脱颗粒（CD107表达）没有变化。相比之下，CD95受体的表达在aMCI和mAD中增加。颗粒酶B的表达和细胞因子产生（TNFα、IFNγ）在aMCI中增加，但在mAD中没有增加。尽管CCR7的表达在aMCI中增加，但aMCI和mAD中CCL19依赖性趋化作用降低，而CCL21依赖性趋化作用未降低。我们的数据表明，与mAD患者相比，aMCI外周NK细胞中观察到的变化数量代表一种激活状态，这可能反映了针对尚待确定的侵袭的活跃免疫反应。
