Kaszubowska Lucyna, Foerster Jerzy, Kwiatkowski Przemysław, Schetz Daria
Department of Histology, Medical University of Gdańsk, Dębinki 1, 80-211 Gdańsk, Poland.
Folia Histochem Cytobiol. 2018;56(4):231-240. doi: 10.5603/FHC.a2018.0025.
NKT-like cells are "non-classical", "CD1d-independent" NKT cells which represent highly differentiated, conventional T lymphocytes coexpressing several NK (natural killer) associated receptors. They are effector lymphocytes of both innate and adaptive immunity and simultaneously regulatory cells of the adaptive immune system. They reveal large granular lymphocyte morphology and can mediate both MHC-restricted and MHC-unrestricted cytotoxicity, secrete many cytokines and modulate Th1 immune responses. The aim of our study was to analyze the expression of proteins involved in cellular stress response: sirtuin 1 (SIRT1), heat shock protein 70 (HSP70) and manganese superoxide dismutase (SOD2) in NKT-like cells compared to T lymphocytes during ageing.
The study involved three groups of participants: the oldest seniors (n = 25; aged over 85; mean age 88 ± 0.5 ys), the old (n = 30; aged under 85; mean age 76 ± 0.9 ys) and the young (n = 32; mean age 21 ± 0.3 ys). Whole blood samples were analyzed by flow cytometry to assess the NKT-like (CD3+CD56+) and T (CD3+) cell populations.
The group of the oldest seniors differed from the other age groups by much higher percentage of both NKT-like cells and T lymphocytes expressing SIRT1, HSP70 and SOD2. The expression of these proteins correlated positively with the age of the participants. Interestingly, the significantly higher expression of the studied protective proteins; i.e. HSP70 and SOD2 was found in CD3+CD56+ cells compared to CD3+ lymphocytes and this phenomenon concerned all the studied age groups. These differences were not significant regarding the expression of SIRT1; however, the same tendency was noticeable.
The analysis of CD3+ and CD3+CD56+ lymphocytes showed the increase in the number of NKT-like cells and decreased number of T cells in the process of ageing. The increased expression of cellular protective proteins SIRT1, HSP70 and SOD2 in NKT-like and T-lymphocytes of the oldest seniors seems to correspond to longevity and the observed correlations may suggest the involvement of these proteins in establishing cellular homeostasis specific for healthy ageing. Furthermore, the higher expression of the protective proteins in NKT-like cells compared to T lymphocytes may indicate their particular role in the interplay between innate and adaptive immunity responses during the process of ageing.
自然杀伤T细胞样细胞是“非经典的”、“不依赖CD1d的”自然杀伤T细胞，代表高度分化的常规T淋巴细胞，共表达几种自然杀伤（NK）相关受体。它们是先天性和适应性免疫的效应淋巴细胞，同时也是适应性免疫系统的调节细胞。它们呈现大颗粒淋巴细胞形态，可介导MHC限制性和MHC非限制性细胞毒性，分泌多种细胞因子并调节Th1免疫反应。我们研究的目的是分析与衰老过程中的T淋巴细胞相比，自然杀伤T细胞样细胞中参与细胞应激反应的蛋白质的表达：沉默调节蛋白1（SIRT1）、热休克蛋白70（HSP70）和锰超氧化物歧化酶（SOD2）。
该研究涉及三组参与者：最年长的老年人（n = 25；年龄超过85岁；平均年龄88±0.5岁）、老年人（n = 30；年龄低于85岁；平均年龄76±0.9岁）和年轻人（n = 32；平均年龄21±0.3岁）。通过流式细胞术分析全血样本，以评估自然杀伤T细胞样（CD3 + CD56 +）和T（CD3 +）细胞群体。
最年长的老年人组与其他年龄组的不同之处在于，表达SIRT1、HSP70和SOD2的自然杀伤T细胞样细胞和T淋巴细胞的百分比要高得多。这些蛋白质的表达与参与者的年龄呈正相关。有趣的是，与CD3 +淋巴细胞相比，在CD3 + CD56 +细胞中发现所研究的保护性蛋白质（即HSP70和SOD2）的表达明显更高，并且这种现象涉及所有研究的年龄组。关于SIRT1的表达，这些差异不显著；然而，相同的趋势是明显的。
对CD3 +和CD3 + CD56 +淋巴细胞的分析表明，在衰老过程中自然杀伤T细胞样细胞数量增加，T细胞数量减少。最年长的老年人的自然杀伤T细胞样细胞和T淋巴细胞中细胞保护性蛋白质SIRT1、HSP70和SOD2表达的增加似乎与长寿相对应，并且观察到的相关性可能表明这些蛋白质参与建立健康衰老特有的细胞稳态。此外，与T淋巴细胞相比，自然杀伤T细胞样细胞中保护性蛋白质的更高表达可能表明它们在衰老过程中先天性和适应性免疫反应之间的相互作用中具有特殊作用。
