幼儿在感染 SARS-CoV-2 后会产生明显的记忆 CD4 T 细胞和记忆 B 细胞反应。

Preschool-age children maintain a distinct memory CD4 T cell and memory B cell response after SARS-CoV-2 infection.

机构信息

Université Paris Cité, INSERM U1151, CNRS UMR8253, Institut Necker Enfants Malades-INEM, F-75015 Paris, France.

Action thématique incitative sur programme-Avenir Team, Auto-Immune and Immune B cells, F-75015 Paris, France.

出版信息

Sci Transl Med. 2024 Sep 18;16(765):eadl1997. doi: 10.1126/scitranslmed.adl1997.

Abstract

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 CD3CD4CD154 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.

摘要

人类免疫系统的发育在出生后持续数年。这种成熟阶段对适应性免疫的质量以及在年幼时感染后获得免疫记忆的影响尚未完全确定。在这里,我们使用抗原反应性 T 细胞(ARTE)测定和多维流式细胞术,在感染之前、感染期间和感染 11 个月后,对儿童和成人循环中严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)反应性 CD3+CD4+CD154+T 细胞进行了分析,将儿童分为单独的年龄组,根据疾病严重程度将成人分为不同的年龄组。在 SARS-CoV-2 感染期间,5 岁以下的儿童表现出较低的抗病毒 CD4 T 细胞反应,而 5 岁以上的儿童和轻症成年人的病毒反应性 CD4 T 细胞反应在数量和表型上具有可比性。重症成年人产生的反应以更高频率的病毒反应性促炎和细胞毒性 T 细胞为特征。在 SARS-CoV-2 感染后,学龄前儿童不仅在感染后维持与成年人相当的中和 SARS-CoV-2 反应性抗体,而且具有表型上不同的记忆 T 细胞,表现出高炎症特征和与向炎症部位迁移相关的特性。此外,学龄前儿童的循环病毒反应性记忆 B 细胞明显少于其他队列。总的来说,我们的结果揭示了年幼个体抗病毒免疫的独特方面,并表明针对 SARS-CoV-2 的适应性反应向成人样表型的成熟是一个渐进的过程。

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