Human NK cells display major phenotypic and functional changes over the life span
Human NK cells display major phenotypic and functional changes over the life span
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DOI：
10.1111/j.1474-9726.2010.00584.x
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发表时间：
2010-08-01
期刊：
影响因子：
7.8
通讯作者：
Vieillard, Vincent
中科院分区：
文献类型：
--
作者：
Le Garff-Tavernier, Magali;Beziat, Vivien;Vieillard, Vincent
衰老通常与感染性疾病和癌症的易感性增加有关，部分与免疫衰老的发展有关，这是一个影响免疫系统所有细胞区室的过程。尽管许多研究调查了年龄对自然杀伤（NK）细胞的影响，但他们的结论仍然存在争议，因为研究对象的不同健康状况导致了不一致的结果。为了阐明这一情况，我们对健康受试者的NK细胞进行了首次广泛的表型和功能分析，比较了来自新生儿（脐带血）、中年（18-60岁）、老年（60-80岁）和极老年（80-100岁）受试者的NK细胞。我们发现，脐带血中的NK细胞显示出与不成熟相关的特定特征，包括KIR和LIR-1/ILT-2的低表达以及NKG 2A和IFN-γ的高表达。另一方面，来自老年受试者的NK细胞保留了其主要的表型和功能特征，但其成熟特征突出。这些包括CD 56 bright亚群的显著下降，LIR-1/ILT-2的特异性增加，以及在非常老的受试者中IL 2活化后NK细胞功能的完美恢复。我们的结论是，NK细胞功能的保存，直到非常先进的年龄可能有助于长寿和成功的老化。
P>Aging is generally associated with an increased predisposition to infectious diseases and cancers, related in part to the development of immune senescence, a process that affects all cell compartments of the immune system. Although many studies have investigated the effects of age on natural killer (NK) cells, their conclusions remain controversial because the diverse health status of study subjects resulted in discordant findings. To clarify this situation, we conducted the first extensive phenotypic and functional analysis of NK cells from healthy subjects, comparing NK cells derived from newborn (cord blood), middle-aged (18-60 years), old (60-80 years), and very old (80-100 years) subjects. We found that NK cells in cord blood displayed specific features associated with immaturity, including poor expression of KIR and LIR-1/ILT-2 and high expression of both NKG2A and IFN-gamma. NK cells from older subjects, on the other hand, preserved their major phenotypic and functional characteristics, but with their mature features accentuated. These include a profound decline of the CD56bright subset, a specific increase in LIR-1/ILT-2, and a perfect recovering of NK-cell function following IL2-activation in very old subjects. We conclude that the preservation of NK cell features until very advanced age may contribute to longevity and successful aging.