Université catholique de Louvain and Cliniques Universitaires Saint-Luc, Laboratory of Pediatric Hepatology and Cell Therapy, PEDI Unit, Brussels, Belgium.
Clin Exp Immunol. 2010 Dec;162(3):494-9. doi: 10.1111/j.1365-2249.2010.04267.x. Epub 2010 Oct 21.
Previous studies have suggested that the susceptibility of newborns to infections is linked to the immaturity of their immune system, but very few data are available on the early stages of maturation of the immune response. Therefore, we decided to investigate the evolution of the interferon (IFN)-α and interleukin (IL)-10 responses in neonatal mononuclear cells. To this end, mononuclear cells isolated from cord blood and peripheral blood of 2-, 6- and 18-month-old children and adults were stimulated with unmethylated cytosine-phosphate-guanosine oligodeoxynucleotide (CpG-ODN) 2216 (IFN-α response) or lipopolysaccharide (LPS) (IL-10 response) for 24 h. The production of IFN-α and IL-10 was then measured in culture supernatants using enzyme-linked immunosorbent assay (ELISA) or a 6-plex cytokine array, respectively. Compared to adults, we found a significant impairment in both the IFN-α and IL-10 responses of neonatal mononuclear cells. Interestingly, both responses had increased significantly after 2 months, but remained lower than the adult responses throughout the first 18 months of life. This study shows that although the immune response of neonates tends to mature fairly quickly, it remains different when compared to the adult immune response throughout the first 18 months of life. This could have important consequences on children's ability to mount an appropriate immune response to various challenges and to establish tolerance and immune homeostasis.
先前的研究表明,新生儿易感染与其免疫系统不成熟有关,但有关免疫应答早期成熟的数据非常有限。因此,我们决定研究新生儿单核细胞中干扰素(IFN)-α和白细胞介素(IL)-10反应的演变。为此,我们从脐带血和 2 个月、6 个月和 18 个月大的儿童以及成年人外周血中分离出单核细胞,用未甲基化的胞嘧啶-磷酸-鸟嘌呤寡脱氧核苷酸(CpG-ODN)2216(IFN-α 反应)或脂多糖(LPS)(IL-10 反应)刺激 24 小时。然后使用酶联免疫吸附测定(ELISA)或 6 合 1 细胞因子阵列分别测量培养上清液中 IFN-α 和 IL-10 的产生。与成年人相比,我们发现新生儿单核细胞的 IFN-α 和 IL-10 反应均明显受损。有趣的是,这两种反应在 2 个月后均显著增加,但在生命的头 18 个月内仍低于成人反应。本研究表明,尽管新生儿的免疫应答趋于快速成熟,但在生命的头 18 个月内与成人免疫应答仍存在差异。这可能对儿童对各种挑战产生适当免疫应答以及建立耐受和免疫稳态的能力产生重要影响。