Phenotype and kinetics of SARS-CoV-2-specific T cells in COVID-19 patients with acute respiratory distress syndrome
Phenotype and kinetics of SARS-CoV-2-specific T cells in COVID-19 patients with acute respiratory distress syndrome
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DOI：
10.1126/sciimmunol.abd2071
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发表时间：
2020-06-01
影响因子：
24.8
通讯作者：
de Vries, Rory D.
中科院分区：
文献类型：
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作者：
Weiskopf, Daniela;Schmitz, Katharina S.;de Vries, Rory D.
SARS-CoV-2 已被确定为全球呼吸道疾病 (COVID-19) 暴发的病原体。在一些患者中，感染会导致中度至重度急性呼吸窘迫综合征（ARDS），需要有创机械通气。高血清水平的 IL-6、IL-10 和被称为“细胞因子风暴”的免疫高反应性与不良的临床结果相关。尽管有大量的 COVID-19 病例和死亡，但有关 SARS-CoV-2 特异性 T 细胞的表型和动力学的信息仍然有限。在这里，我们研究了 10 名需要入住重症监护室的 COVID-19 患者，并分别在 10 名患者中的 10 名和每 10 名患者中的 8 名中检测到 SARS-CoV-2 特异性 CD4(+) 和 CD8(+) T 细胞。我们还在之前未接触过 SARS-CoV-2 的健康对照者中检测到 SARS-CoV-2 反应性 T 细胞水平较低，这表明由于过去感染过“普通感冒”冠状病毒而存在交叉反应。最强的 T 细胞反应针对刺突 (S) 表面糖蛋白，SARS-CoV-2 特异性 T 细胞主要产生效应细胞因子和 Th1 细胞因子，尽管也检测到 Th2 和 Th17 细胞因子。此外，我们研究了 T 细胞动力学，结果表明 SARS-CoV-2 特异性 T 细胞出现相对较早，并随着时间的推移而增加。总的来说，这些数据揭示了 T 细胞反应作为疾病严重程度函数的潜在变化，这是理解免疫病理学在疾病中潜在作用的关键问题，也为疫苗设计和评估提供了信息。
SARS-CoV-2 has been identified as the causative agent of a global outbreak of respiratory tract disease (COVID-19). In some patients the infection results in moderate to severe acute respiratory distress syndrome (ARDS), requiring invasive mechanical ventilation. High serum levels of IL-6, IL-10 and an immune hyperresponsiveness referred to as a 'cytokine storm' have been associated with poor clinical outcome. Despite the large numbers of COVID-19 cases and deaths, information on the phenotype and kinetics of SARS-CoV-2-specific T cells is limited. Here, we studied 10 COVID-19 patients who required admission to an intensive care unit and detected SARS-CoV-2-specific CD4(+) and CD8(+) T cells in 10 out of 10 and 8 out of 10 patients, respectively. We also detected low levels of SARS-CoV-2-reactive T cells in 2 out of 10 healthy controls not previously exposed to SARS-CoV-2, which is indicative of cross-reactivity due to past infection with 'common cold' coronaviruses. The strongest T-cell responses were directed to the spike (S) surface glycoprotein, and SARS-CoV-2-specific T cells predominantly produced effector and Th1 cytokines, although Th2 and Th17 cytokines were also detected. Furthermore, we studied T-cell kinetics and showed that SARS-CoV-2-specific T cells are present relatively early and increase over time. Collectively, these data shed light on the potential variations in T-cell responses as a function of disease severity, an issue that is key to understanding the potential role of immunopathology in the disease, and also inform vaccine design and evaluation.