Proinflammatory T Cell Status Associated with Early Life Adversity
Proinflammatory T Cell Status Associated with Early Life Adversity
复制标题
DOI：
10.4049/jimmunol.1701082
复制
发表时间：
2017-12-15
影响因子：
4.4
通讯作者：
Muller, Claude P.
中科院分区：
文献类型：
--
作者：
Elwenspoek, Martha M. C.;Hengesch, Xenia;Muller, Claude P.
早期生活逆境(ELA)与疾病风险的增加有关，而免疫系统在其中起着关键作用。ELA的免疫表型以炎症、细胞免疫受损和免疫衰老为特征。然而，关于细胞特异性免疫效应的数据在很大程度上是缺乏的。此外，应激系统和健康行为在ELA中发生改变，这可能有助于ELA免疫表型的产生。本研究测试了ELA患者(n=42)和无ELA病史者(n=73)的细胞特异性免疫差异与ELA免疫表型、改变的应激参数和健康行为的关系。用流式细胞仪检测单核细胞、NK细胞、B细胞、T细胞及其主要亚群的相对数量和活化状态(CD25、CD69、HLA-DR、CD11a、CD11b)。ELA与CD69(+)CD8(+)T细胞数量显著减少(p=0.022)，人类白细胞抗原-DR+CD4和人类白细胞抗原-DR+CD8T细胞数量增加(p=0.001)以及CD25(+)CD8(+)T细胞数量增加(p=0.036)相关。ELA还表现出CCR4(+)、CXCR3(-)、CCR6(+)CD4T细胞数量增加的趋势。综上所述，我们的数据表明ELA的免疫激活状态升高，特别是T细胞受到影响。尽管ELA免疫表型的几个方面与激活标志物的增加有关，但无论是应激还是健康危险行为都不能解释观察到的群体差异。因此，ELA中的免疫激活状态似乎不是应激系统或健康危险行为变化的次要因素，而是早期生命规划对免疫细胞的主要影响。
Early life adversity (ELA) has been associated with an increased risk for diseases in which the immune system plays a critical role. The ELA immune phenotype is characterized by inflammation, impaired cellular immunity, and immunosenescence. However, data on cell-specific immune effects are largely absent. Additionally, stress systems and health behaviors are altered in ELA, which may contribute to the generation of the ELA immune phenotype. The present investigation tested cell-specific immune differences in relationship to the ELA immune phenotype, altered stress parameters, and health behaviors in individuals with ELA (n = 42) and those without a history of ELA (control, n = 73). Relative number and activation status (CD25, CD69, HLA-DR, CD11a, CD11b) of monocytes, NK cells, B cells, T cells, and their main subsets were assessed by flow cytometry. ELA was associated with significantly reduced numbers of CD69(+) CD8(+) T cells (p = 0.022), increased numbers of HLA-DR+ CD4 and HLA-DR+ CD8 T cells (p < 0.001), as well as increased numbers of CD25(+) CD8(+) T cells (p = 0.036). ELA also showed a trend toward higher numbers of CCR4(+) CXCR3(-) CCR6(+) CD4 T cells. Taken together, our data suggest an elevated state of immune activation in ELA, in which particularly T cells are affected. Although several aspects of the ELA immune phenotype were related to increased activation markers, neither stress nor health-risk behaviors explained the observed group differences. Thus, the state of immune activation in ELA does not seem to be secondary to alterations in the stress system or health-risk behaviors, but rather a primary effect of early life programming on immune cells.