McDade T W, Jones M J, Miller G, Borja J, Kobor M S, Kuzawa C W
1Department of Anthropology,Northwestern University,Evanston,IL,USA.
4BC Children's Hospital Research Institute,University of British Columbia,Vancouver,BC,Canada.
J Dev Orig Health Dis. 2018 Apr;9(2):198-207. doi: 10.1017/S2040174417000794. Epub 2017 Oct 11.
The immune system not only provides protection against infectious disease but also contributes to the etiology of neoplastic, atopic, and cardiovascular and metabolic diseases. Prenatal and postnatal nutritional and microbial environments have lasting effects on multiple aspects of immunity, indicating that immune processes may play important roles in the developmental origins of disease. The objective of this study is to evaluate the association between birth weight and the distribution of leukocyte (white blood cell) subsets in peripheral blood in young adulthood. Postnatal microbial exposures were also considered as predictors of leukocyte distribution. Participants (n=486; mean age=20.9 years) were drawn from a prospective birth cohort study in the Philippines, and analyses focused on the following cell types: CD4 T lymphocytes, CD8 T lymphocytes, B lymphocytes, natural killer cells, monocytes, granulocytes. Higher birth weight was a strong predictor of higher proportion of CD4 T lymphocytes (B=0.12, s.e.=0.041, P=0.003), lower proportion of CD8 T lymphocytes (B=-0.874, s.e.=0.364, P=0.016), higher CD4:CD8 ratio (B=1.964, s.e.=0.658, P=0.003), and higher B lymphocytes (B=0.062, s.e.=0.031, P=0.047). Measures of microbial exposure in infancy were negatively associated with proportions of B lymphocytes and granulocytes, and lower CD4:CD8 ratio. Leukocytes are the key regulators and effectors of innate and specific immunity, but the origins of variation in the distribution of cell type across individuals are not known. Our findings point toward nutritional and microbial exposures in infancy as potentially important determinants of immune-phenotypes in adulthood, and they suggest that leukocyte distribution is a plausible mechanism through which developmental environments have lasting effects on disease risk in adulthood.
免疫系统不仅能抵御传染病,还在肿瘤、特应性疾病以及心血管和代谢疾病的病因学中发挥作用。产前和产后的营养及微生物环境对免疫的多个方面具有持久影响,这表明免疫过程可能在疾病的发育起源中发挥重要作用。本研究的目的是评估出生体重与青年期外周血白细胞(白血球)亚群分布之间的关联。产后微生物暴露也被视为白细胞分布的预测因素。参与者(n = 486;平均年龄 = 20.9岁)来自菲律宾的一项前瞻性出生队列研究,分析聚焦于以下细胞类型:CD4 T淋巴细胞、CD8 T淋巴细胞、B淋巴细胞、自然杀伤细胞、单核细胞、粒细胞。较高的出生体重是CD4 T淋巴细胞比例较高(B = 0.12,标准误 = 0.041,P = 0.003)、CD8 T淋巴细胞比例较低(B = -0.874,标准误 = 0.364,P = 0.016)、CD4:CD8比值较高(B = 1.964,标准误 = 0.658,P = 0.003)以及B淋巴细胞比例较高(B = 0.062,标准误 = 0.031,P = 0.047)的有力预测因素。婴儿期微生物暴露的测量值与B淋巴细胞和粒细胞的比例以及较低的CD4:CD8比值呈负相关。白细胞是先天性和特异性免疫的关键调节因子和效应器,但个体间细胞类型分布差异的起源尚不清楚。我们的研究结果表明,婴儿期的营养和微生物暴露可能是成年期免疫表型的重要决定因素,并且提示白细胞分布是发育环境对成年期疾病风险产生持久影响的一种合理机制。