The development of the human immune system lasts for several years after birth. The impact of this maturation phase on the quality of adaptive immunity and the acquisition of immunological memory after infection at a young age remains incompletely defined. Here, using an antigen-reactive T cell (ARTE) assay and multidimensional flow cytometry, we profiled circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–reactive CD3 + CD4 + CD154 + T cells in children and adults before infection, during infection, and 11 months after infection, stratifying children into separate age groups and adults according to disease severity. During SARS-CoV-2 infection, children younger than 5 years old displayed a lower antiviral CD4 + T cell response, whereas children older than 5 years and adults with mild disease had, quantitatively and phenotypically, comparable virus-reactive CD4 + T cell responses. Adults with severe disease mounted a response characterized by higher frequencies of virus-reactive proinflammatory and cytotoxic T cells. After SARS-CoV-2 infection, preschool-age children not only maintained neutralizing SARS-CoV-2–reactive antibodies postinfection comparable to adults but also had phenotypically distinct memory T cells displaying high inflammatory features and properties associated with migration toward inflamed sites. Moreover, preschool-age children had markedly fewer circulating virus-reactive memory B cells compared with the other cohorts. Collectively, our results reveal unique facets of antiviral immunity in humans at a young age and indicate that the maturation of adaptive responses against SARS-CoV-2 toward an adult-like profile occurs in a progressive manner.

中文翻译：

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学龄前儿童在 SARS-CoV-2 感染后保持独特的记忆 CD4 + T 细胞和记忆 B 细胞反应


人体免疫系统的发育在出生后持续数年。这个成熟阶段对年轻时感染后适应性免疫质量和免疫记忆获得的影响仍未完全确定。在这里，使用抗原反应性 T 细胞 （ARTE） 测定和多维流式细胞术，我们分析了儿童和成人在感染前、感染期间和感染后 11 个月循环的严重急性呼吸系统综合症冠状病毒 2 （SARS-CoV-2） 反应性 CD3 + CD4 + CD154 + T 细胞，根据疾病严重程度将儿童分为不同的年龄组和成人。在 SARS-CoV-2 感染期间，5 岁以下儿童表现出较低的抗病毒 CD4 + T 细胞反应，而 5 岁以上儿童和轻度疾病成人在数量和表型上具有相当的病毒反应性 CD4 + T 细胞反应。患有严重疾病的成年人的反应以病毒反应性促炎和细胞毒性 T 细胞的频率较高为特征。SARS-CoV-2 感染后，学龄前儿童不仅在感染后保持与成人相当的中和 SARS-CoV-2 反应性抗体，而且具有表型不同的记忆 T 细胞，显示出与迁移到发炎部位相关的高炎症特征和特性。此外，与其他队列相比，学龄前儿童的循环病毒反应性记忆 B 细胞明显较少。总的来说，我们的结果揭示了人类年轻时抗病毒免疫的独特方面，并表明对 SARS-CoV-2 的适应性反应以渐进的方式成熟为成人样。