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儿童和轻症 COVID-19 患者:记忆 T 细胞反应长达 10 个月的动态变化。

Children and Adults With Mild COVID-19: Dynamics of the Memory T Cell Response up to 10 Months.

机构信息

Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands.

Faculty of Veterinary Medicine, Utrecht University, Utrecht, Netherlands.

出版信息

Front Immunol. 2022 Feb 7;13:817876. doi: 10.3389/fimmu.2022.817876. eCollection 2022.

Abstract

BACKGROUND

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to considerable morbidity/mortality worldwide, but most infections, especially among children, have a mild course. However, it remains largely unknown whether infected children develop cellular immune memory.

METHODS

To determine whether a memory T cell response is being developed, we performed a longitudinal assessment of the SARS-CoV-2-specific T cell response by IFN-γ ELISPOT and activation marker analyses of peripheral blood samples from unvaccinated children and adults with mild-to-moderate COVID-19.

RESULTS

Upon stimulation of PBMCs with heat-inactivated SARS-CoV-2 or overlapping peptides of spike (S-SARS-CoV-2) and nucleocapsid proteins, we found S-SARS-CoV-2-specific IFN-γ T cell responses in infected children (83%) and adults (100%) that were absent in unexposed controls. Frequencies of SARS-CoV-2-specific T cells were higher in infected adults, especially several cases with moderate symptoms, compared to infected children. The S-SARS-CoV-2 IFN-γ T cell response correlated with S1-SARS-CoV-2-specific serum antibody concentrations. Predominantly, effector memory CD4+ T cells of a Th1 phenotype were activated upon exposure to SARS-CoV-2 antigens. Frequencies of SARS-CoV-2-specific T cells were significantly reduced at 10 months after symptom onset, while S1-SARS-CoV-2-specific IgG concentrations were still detectable in 90% of all children and adults.

CONCLUSIONS

Our data indicate that an antigen-specific T cell and antibody response is developed after mild SARS-CoV-2 infection in children and adults. It remains to be elucidated to what extent this SARS-CoV-2-specific response can contribute to an effective recall response after reinfection.

摘要

背景

严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)已在全球范围内导致大量发病率/死亡率,但大多数感染,尤其是儿童,其病程较轻。然而,目前尚不清楚感染儿童是否会产生细胞免疫记忆。

方法

为了确定是否正在产生记忆 T 细胞反应,我们通过 IFN-γ ELISPOT 和外周血样本中激活标志物分析,对未接种疫苗的轻度至中度 COVID-19 儿童和成人的 SARS-CoV-2 特异性 T 细胞反应进行了纵向评估。

结果

在用热灭活的 SARS-CoV-2 或刺突(S-SARS-CoV-2)和核衣壳蛋白的重叠肽刺激 PBMC 后,我们在感染儿童(83%)和成人(100%)中发现了 S-SARS-CoV-2 特异性 IFN-γ T 细胞反应,而在未暴露对照中则不存在。与感染儿童相比,感染成人的 SARS-CoV-2 特异性 T 细胞频率更高,尤其是一些症状中度的病例。S-SARS-CoV-2 IFN-γ T 细胞反应与 S1-SARS-CoV-2 特异性血清抗体浓度相关。在接触 SARS-CoV-2 抗原后,主要是 Th1 表型的效应记忆 CD4+T 细胞被激活。在症状出现后 10 个月,SARS-CoV-2 特异性 T 细胞的频率显著降低,而在所有儿童和成人中,S1-SARS-CoV-2 特异性 IgG 浓度仍可检测到 90%。

结论

我们的数据表明,在儿童和成人中,轻度 SARS-CoV-2 感染后会产生抗原特异性 T 细胞和抗体反应。仍有待阐明这种 SARS-CoV-2 特异性反应在再次感染后能在多大程度上引起有效的回忆反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b78/8858984/72f58fed147d/fimmu-13-817876-g001.jpg

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