SARS-CoV-2-reactive T cells in healthy donors and patients with COVID-19
SARS-CoV-2-reactive T cells in healthy donors and patients with COVID-19
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DOI：
10.1038/s41586-020-2598-9
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发表时间：
2020-07-29
期刊：
影响因子：
64.8
通讯作者：
Thiel, Andreas
中科院分区：
文献类型：
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作者：
Braun, Julian;Loyal, Lucie;Thiel, Andreas
一项针对COVID-19患者和健康供体的研究发现，CD4(+)T细胞对SARS-CoV-2和人类地方性冠状病毒的刺突蛋白有反应；然而，预先存在的SARS-CoV-2交叉反应性T细胞对临床结果的影响仍有待确定。严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）引起了迅速展开的冠状病毒病2019 （COVID-19）大流行（1,2）。COVID-19的临床表现各不相同，从无症状感染到呼吸衰竭。决定这些可变结果的机制仍未得到解决。在这里，我们研究了COVID-19患者和未暴露于SARS-CoV-2的健康供者外周血中对SARS-CoV-2刺突糖蛋白有反应的CD4(+)T细胞。我们不仅在83%的COVID-19患者中检测到尖峰反应性CD4(+)T细胞，而且在35%的健康供体中也检测到。健康供体的刺突反应性CD4(+)T细胞主要对刺突蛋白的c端表位具有活性，与n端表位相比，c端表位与人地方性冠状病毒刺突糖蛋白具有更高的同源性。从未感染SARS-CoV-2的健康供体产生的刺突蛋白反应性T细胞系对人类地方性冠状病毒229E和OC43以及SARS-CoV-2的刺突蛋白的c端区域有类似的反应。这一结果表明存在刺蛋白交叉反应性T细胞，这可能是在以前与地方性冠状病毒接触时产生的。预先存在的SARS-CoV-2交叉反应性T细胞对临床结果的影响仍有待在更大的队列中确定。然而，在相当一部分普通人群中存在刺突蛋白交叉反应性T细胞可能会影响当前大流行的动态，并对即将开展的COVID-19疫苗试验的设计和分析具有重要意义。
A study of patients with COVID-19 and healthy donors found CD4(+)T cells that react to the spike protein of SARS-CoV-2 and human endemic coronaviruses; however, the effect of pre-existing SARS-CoV-2 cross-reactive T cells on clinical outcomes remains to be determined.Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the rapidly unfolding coronavirus disease 2019 (COVID-19) pandemic(1,2). Clinical manifestations of COVID-19 vary, ranging from asymptomatic infection to respiratory failure. The mechanisms that determine such variable outcomes remain unresolved. Here we investigated CD4(+)T cells that are reactive against the spike glycoprotein of SARS-CoV-2 in the peripheral blood of patients with COVID-19 and SARS-CoV-2-unexposed healthy donors. We detected spike-reactive CD4(+)T cells not only in 83% of patients with COVID-19 but also in 35% of healthy donors. Spike-reactive CD4(+)T cells in healthy donors were primarily active against C-terminal epitopes in the spike protein, which show a higher homology to spike glycoproteins of human endemic coronaviruses, compared with N-terminal epitopes. Spike-protein-reactive T cell lines generated from SARS-CoV-2-naive healthy donors responded similarly to the C-terminal region of the spike proteins of the human endemic coronaviruses 229E and OC43, as well as that of SARS-CoV-2. This results indicate that spike-protein cross-reactive T cells are present, which were probably generated during previous encounters with endemic coronaviruses. The effect of pre-existing SARS-CoV-2 cross-reactive T cells on clinical outcomes remains to be determined in larger cohorts. However, the presence of spike-protein cross-reactive T cells in a considerable fraction of the general population may affect the dynamics of the current pandemic, and has important implications for the design and analysis of upcoming trials investigating COVID-19 vaccines.