During the period of transition from intrauterine to extrauterine life, the neonatal immune system must learn to rapidly identify pathogens while balancing pro-inflammatory, antimicrobial responses with immune regulation that allows for resolution of inflammation and limits responses to commensal organisms and benign environmental antigens. However, the naive immune system of neonates is presented with several barriers that limit robust proinflammatory immune responses. Specifically, epigenetic modifications to neonatal naive CD4+ T cells, heightened neonatal regulatory T cell frequency and function, and limitations in the co-stimulatory potential of neonatal antigen presenting cells restrict development of CD4+ T cells with a T-helper 1 type functional profile. This restriction likely contributes to the increased risk of severe infection observed during early life. New research, however, suggests that neonates are capable of utilizing unique compensatory mechanisms to circumvent these restrictions and generate T-helper 1 type immunity under some circumstances. Understanding how to manipulate the immune responses of young infants to optimize development of T-helper 1 type immunity is key to the development of immune-based treatments and prevention strategies for severe infections in this vulnerable population.

中文翻译：

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新生儿期的CD4 + T细胞活化：针对Th1免疫的障碍和途径。

在从宫内到宫外生活的过渡期间，新生儿免疫系统必须学会快速识别病原体，同时平衡促炎，抗菌反应和免疫调节，以调节炎症并限制对共生生物和良性环境抗原的应答。但是，新生儿的天然免疫系统存在一些障碍，这些障碍限制了强大的促炎性免疫反应。具体而言，对新生儿朴素的CD4 + T细胞的表观遗传修饰，新生儿调节性T细胞的频率和功能增强以及新生儿抗原呈递细胞的共刺激潜力受到限制，从而限制了具有T辅助1型功能谱的CD4 + T细胞的发育。这种限制可能导致在生命早期发现严重感染的风险增加。然而，新的研究表明，新生儿能够利用独特的补偿机制来规避这些限制，并在某些情况下产生T-helper 1型免疫。了解如何操纵婴幼儿的免疫反应以优化T-helper 1型免疫的发展，是开发基于免疫的治疗方法和针对该弱势人群严重感染的预防策略的关键。