Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands.
Faculty of Veterinary Medicine, Utrecht University, Utrecht, Netherlands.
Front Immunol. 2022 Feb 7;13:817876. doi: 10.3389/fimmu.2022.817876. eCollection 2022.
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.
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.
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.
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.
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。
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。
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%。
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。