Age-related changes in natural killer cell repertoires: impact on NK cell function and immune surveillance
Age-related changes in natural killer cell repertoires: impact on NK cell function and immune surveillance
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DOI：
10.1007/s00262-015-1750-0
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发表时间：
2016-04-01
影响因子：
5.8
通讯作者：
Uhrberg, Markus
中科院分区：
文献类型：
--
作者：
Manser, Angela R.;Uhrberg, Markus
人自然杀伤（NK）细胞的一个关键特征是表达KIR和NKG 2基因家族的HLA I类特异性受体，其能够有效识别感染的和恶性的靶细胞。受体表达的细胞间变异性导致复杂NK细胞库的形成。如本文所述，NK细胞从新生儿到成人经历了主要变化，其特征在于抑制性NKG 2A受体下调和伴随的KIR家族成员上调。这个过程在年轻人中完成，并且在大多数个体中，KIR/NKG 2A库保持非常稳定，直到老年。尽管如此，年龄相关因素有可能主要影响NK细胞库的复杂性：首先，HCMV感染与某些个体中表达终末分化NKG 2C和KIR的NK细胞的主要克隆扩增相关。其次，无效的造血可导致不成熟和较少多样化的NK细胞库，如在骨髓增生异常综合征（MDS）（一种老年人的恶性疾病）中观察到的。因此，尽管在大多数老年人中，NK细胞区室在功能和表型方面似乎是高度稳定的，但在少数受试者中观察到NK细胞库多样性的分解，这可能影响免疫监视和健康衰老。
A key feature of human natural killer (NK) cells, which enables efficient recognition of infected and malignant target cells, is the expression of HLA class I-specific receptors of the KIR and NKG2 gene families. Cell-to-cell variability in receptor expression leads to the formation of complex NK cell repertoires. As outlined here, NK cells go through major changes from newborns to adults characterized by downregulation of the inhibitory NKG2A receptor and concomitant upregulation of KIR family members. This process is completed in young adults, and in the majority of individuals, KIR/NKG2A repertoires remain remarkably stable until old age. Nonetheless, age-related factors have the potential to majorly influence the complexity of NK cell repertoires: Firstly infection with HCMV is associated with major clonal expansions of terminally differentiated NKG2C- and KIR-expressing NK cells in certain individuals. Secondly, ineffective hematopoiesis can lead to immature and less diversified NK cell repertoires as observed in myelodysplastic syndrome (MDS), a malignant disease of the elderly. Thus, whereas in the majority of elderly the NK cell compartment appears to be highly stable in terms of function and phenotype, in a minority of subjects a breakdown of NK cell repertoire diversity is observed that might influence immune surveillance and healthy aging.