Elwenspoek Martha M C, Hengesch Xenia, Leenen Fleur A D, Schritz Anna, Sias Krystel, Schaan Violetta K, Mériaux Sophie B, Schmitz Stephanie, Bonnemberger Fanny, Schächinger Hartmut, Vögele Claus, Turner Jonathan D, Muller Claude P
Department of Infection and Immunity, Luxembourg Institute of Health, 4354 Esch-sur-Alzette, Luxembourg.
Department of Immunology, Research Institute of Psychobiology, University of Trier, 54290 Trier, Germany.
J Immunol. 2017 Dec 15;199(12):4046-4055. doi: 10.4049/jimmunol.1701082. Epub 2017 Nov 13.
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 ( = 42) and those without a history of ELA (control, = 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 CD69CD8 T cells ( = 0.022), increased numbers of HLA-DR CD4 and HLA-DR CD8 T cells ( < 0.001), as well as increased numbers of CD25CD8 T cells ( = 0.036). ELA also showed a trend toward higher numbers of CCR4CXCR3CCR6 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.
早年生活逆境（ELA）与免疫系统起关键作用的疾病风险增加有关。ELA免疫表型的特征是炎症、细胞免疫受损和免疫衰老。然而，关于细胞特异性免疫效应的数据大多缺失。此外，ELA会改变应激系统和健康行为，这可能有助于ELA免疫表型的产生。本研究测试了ELA个体（n = 42）和无ELA病史个体（对照组，n = 73）中与ELA免疫表型、应激参数改变和健康行为相关的细胞特异性免疫差异。通过流式细胞术评估单核细胞、自然杀伤（NK）细胞、B细胞、T细胞及其主要亚群的相对数量和激活状态（CD25、CD69、HLA-DR、CD11a、CD11b）。ELA与CD69⁺CD8⁺ T细胞数量显著减少（P = 0.022）、HLA-DR⁺ CD4⁺和HLA-DR⁺ CD8⁺ T细胞数量增加（P < 0.001）以及CD25⁺CD8⁺ T细胞数量增加（P = 0.036）有关。ELA还显示出CCR4⁺CXCR3⁻CCR6⁺ CD4⁺ T细胞数量有增加的趋势。综上所述，我们的数据表明ELA中免疫激活状态升高，其中特别是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增加有关，但应激和健康风险行为均无法解释观察到的组间差异。因此，ELA中的免疫激活状态似乎并非继发于应激系统或健康风险行为的改变，而是早年编程对免疫细胞的主要影响。
