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急性呼吸窘迫综合征的 COVID-19 患者中 SARS-CoV-2 特异性 T 细胞的表型和动力学。

Phenotype and kinetics of SARS-CoV-2-specific T cells in COVID-19 patients with acute respiratory distress syndrome.

机构信息

Center for Infectious Disease, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.

Department of Viroscience, Erasmus MC, Rotterdam, the Netherlands.

出版信息

Sci Immunol. 2020 Jun 26;5(48). doi: 10.1126/sciimmunol.abd2071.

Abstract

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.

摘要

严重急性呼吸综合征冠状病毒 2 已被确定为导致全球呼吸道疾病(COVID-19)爆发的病原体。在某些患者中,感染导致中度至重度急性呼吸窘迫综合征(ARDS),需要进行有创机械通气。高水平的白细胞介素 6(IL-6)、白细胞介素 10(IL-10)和被称为“细胞因子风暴”的免疫高反应性与不良临床结局相关。尽管 COVID-19 病例和死亡人数众多,但有关 SARS-CoV-2 特异性 T 细胞表型和动力学的信息有限。在这里,我们研究了 10 名需要入住重症监护病房的 COVID-19 患者,在 10 名患者中的 10 名和 8 名患者中的 8 名患者中检测到了 SARS-CoV-2 特异性 CD4 和 CD8 T 细胞。我们还在 2 名未接触过 SARS-CoV-2 的健康对照者中检测到低水平的 SARS-CoV-2 反应性 T 细胞,这表明由于过去感染了“普通感冒”冠状病毒而发生了交叉反应。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,并表明 SARS-CoV-2 特异性 T 细胞相对较早出现,并随时间增加。总之,这些数据揭示了 T 细胞反应作为疾病严重程度的函数的潜在变化,这是了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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b1ca/7319493/f96ebb570142/abd2071-F1.jpg

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