NK cells are cytotoxic lymphocytes of innate immunity composed of: cytotoxic CD56dim and immunoregulatory CD56bright cells. The study aimed to analyze the expression of cellular protective proteins: sirtuin 1 (SIRT1), heat shock protein 70 (HSP70) and manganese superoxide dismutase (SOD2) in CD56dim and CD56bright NK cells of the young, seniors aged under 85 (‘the old’) and seniors aged over 85 (‘the oldest’). We studied both non-stimulated NK cells and cells stimulated by IL-2, LPS or PMA with ionomycin. The expression level of proinflammatory cytokines TNF and IFN-γ was also assessed in NK cell subsets and some relationships between the studied parameters were analyzed. CD56bright cells showed sensitivity to most of the applied stimulatory agents until very advanced age in regards to the expression of SIRT1 and intracellular HSP70. On the contrary, CD56dim cells, sensitive to stimulation by most of the stimulatory agents in the young and the old, in the oldest lost this sensitivity and presented rather high, constant expression of SIRT1 and HSP70, resistant to further stimulation. With reference to SOD2 expression, CD56dim cells were insensitive to stimulation in the young, but their sensitivity increased with ageing. CD56bright cells were sensitive to most of the applied agents in the young and the old but in the oldest they responded to all of the stimulatory agents used in the study. Similarly, both NK cell subsets were sensitive to stimulation until very advanced age in regards to the expression of TNF and IFN-γ. CD56bright cells maintained sensitivity to stimulation until very advanced age presenting also an increased expression of SIRT1 and HSP70. CD56dim cells showed a constantly increased expression of these cellular protective proteins in the oldest, insensitive for further stimulation. The oldest, however, did not reveal an increased level of SOD2 expression, but it was significantly elevated in both NK cell subsets after stimulation. The pattern of expression of the studied cellular protective proteins in ageing process revealed the adaptation of NK cells to stress response in the oldest seniors which might accompany the immunosenescence and contribute to the long lifespan of this group of the elderly.

中文翻译：

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CD56bright 细胞对刺激有反应，直到非常高龄为止，显示细胞保护蛋白 SIRT1、HSP70 和 SOD2 表达增加

NK 细胞是先天免疫的细胞毒性淋巴细胞，由细胞毒性 CD56dim 和免疫调节 CD56bright 细胞组成。该研究旨在分析细胞保护蛋白：去乙酰化酶1（SIRT1）、热休克蛋白70（HSP70）和锰超氧化物歧化酶（SOD2）在年轻、85岁以下老年人（“老年人”）CD56dim和CD56bright NK细胞中的表达情况。 ”）和 85 岁以上的老年人（“最年长的”）。我们研究了未刺激的 NK 细胞和经 IL-2、LPS 或 PMA 与离子霉素刺激的细胞。还评估了 NK 细胞亚群中促炎细胞因子 TNF 和 IFN-γ 的表达水平，并分析了所研究参数之间的一些关系。CD56bright 细胞在 SIRT1 和细胞内 HSP70 的表达方面对大多数应用的刺激剂表现出敏感性，直到非常高的年龄。相反，CD56dim 细胞在年轻人和老年人中对大多数刺激剂的刺激敏感，但在最年长的人中失去了这种敏感性，并表现出相当高且恒定的 SIRT1 和 HSP70 表达，对进一步的刺激产生抵抗。就SOD2表达而言，CD56dim细胞在年轻时对刺激不敏感，但其敏感性随着年龄的增长而增加。CD56bright 细胞对年轻人和老年人的大多数应用药物敏感，但在最年长的人中，它们对研究中使用的所有刺激剂都有反应。同样，两种 NK 细胞亚群在 TNF 和 IFN-γ 的表达方面对刺激敏感，直到非常高的年龄。CD56bright 细胞一直保持对刺激的敏感性，直到非常高的年龄，SIRT1 和 HSP70 的表达也增加。CD56dim 细胞在最古老的细胞中显示出这些细胞保护蛋白的表达不断增加，对进一步的刺激不敏感。然而，最古老的研究并未显示 SOD2 表达水平增加，但刺激后两个 NK 细胞亚群的 SOD2 表达水平均显着升高。研究的细胞保护蛋白在衰老过程中的表达模式揭示了NK细胞对最年长老年人应激反应的适应，这可能伴随着免疫衰老，并有助于这组老年人的长寿。