Interleukin-8 (CXCL8) production is a signatory T cell effector function of human newborn infants
Interleukin-8 (CXCL8) production is a signatory T cell effector function of human newborn infants
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DOI：
10.1038/nm.3670
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发表时间：
2014-10-01
期刊：
影响因子：
82.9
通讯作者：
Hayday, Adrian
中科院分区：
文献类型：
--
作者：
Gibbons, Deena;Fleming, Paul;Hayday, Adrian
尽管他们与环境的急剧遭遇，新生儿不能容易地安装T辅助1型（T（H）1）细胞抗菌和抗病毒反应。相反，它们显示出向T（H）2反应的倾斜，T（H）2反应与免疫调节功能一起被认为限制了炎症损伤的可能性，同时允许肠道细菌定植（1-3）。然而，这些集体能力占相对较少的T细胞。在这里，我们证明了人类新生儿中的主要T细胞效应功能是白细胞介素-8（CXCL 8）的产生，它具有激活抗微生物中性粒细胞和γ δ T细胞的潜力。CXCL 8的产生是由与这些少数细胞不同的T细胞的抗原受体接合引起的。产生T（H）1、T（H）2和T（H）17细胞因子，由Toll样受体信号传导共刺激，并且在早产儿中很明显，特别是那些经历新生儿感染和严重病理的婴儿。相比之下，产生CXCL 8的T细胞在成年人中很少见，在新生小鼠中没有明显的等效功能。CXCL 8的产生反驳了人们普遍持有的观点，即T淋巴细胞在非常早期的生命中本质上是抗炎的，这对免疫监测、免疫干预（包括疫苗接种）和免疫病理学都有影响。它还强调婴儿和成人免疫系统之间的质的区别。
In spite of their precipitous encounter with the environment, newborn infants cannot readily mount T helper type 1 (T(H)1) cell antibacterial and antiviral responses. Instead, they show skewing toward T(H)2 responses, which, together with immunoregulatory functions, are thought to limit the potential for inflammatory damage, while simultaneously permitting intestinal colonization by commensals(1-3). However, these collective capabilities account for relatively few T cells. Here we demonstrate that a major T cell effector function in human newborns is interleukin-8 (CXCL8) production, which has the potential to activate antimicrobial neutrophils and gamma delta T cells. CXCL8 production was provoked by antigen receptor engagement of T cells that are distinct from those few cells. producing T(H)1, T(H)2 and T(H)17 cytokines, was co-stimulated by Toll-like receptor signaling, and was readily apparent in preterm babies, particularly those experiencing neonatal infections and severe pathology. By contrast, CXCL8-producing T cells were rare in adults, and no equivalent function was evident in neonatal mice. CXCL8 production counters the widely held view that T lymphocytes in very early life are intrinsically anti-inflammatory, with implications for immune monitoring, immune interventions (including vaccination) and immunopathologies. It also emphasizes qualitative distinctions between infants' and adults' immune systems.