Identifying SARS-CoV-2 'memory' NK cells from COVID-19 convalescent donors for adoptive cell therapy.
Identifying SARS-CoV-2 'memory' NK cells from COVID-19 convalescent donors for adoptive cell therapy.
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DOI：
10.1111/imm.13432
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发表时间：
2022-03
期刊：
影响因子：
6.4
通讯作者：
Eguizabal C
中科院分区：
文献类型：
--
作者：
Herrera L;Martin-Inaraja M;Santos S;Inglés-Ferrándiz M;Azkarate A;Perez-Vaquero MA;Vesga MA;Vicario JL;Soria B;Solano C;De Paz R;Marcos A;Ferreras C;Perez-Martinez A;Eguizabal C
COVID-19疾病是冠状病毒2型综合征（SARS-CoV-2）感染的表现，正在引起全球大流行。这种疾病可以导致多种不同的症状，淋巴细胞减少症与最持久的严重程度之一。自然杀伤细胞（NK细胞）是先天免疫系统的一部分，对抗病毒感染的细胞是其关键作用之一。在这项研究中，我们确定了COVID-19后NK细胞的表型以及恢复期供体血液中SARS-CoV-2-特异性NK细胞群的主要特征。SARS-CoV-2恢复期供体中的CD 57 + NKG 2C+表型表明存在“记忆”/活化NK细胞，如巨细胞病毒感染所示。尽管这一群体的存在依赖于供体，但其表达可能对于针对SARS-CoV-2的特异性反应至关重要，因此，它为我们提供了一种选择最佳供体的工具，以生产用于RELEASE临床试验（NCT 04578210）下治疗COVID-19患者的细胞疗法的现成活性药物。SARS-CoV-2感染诱导促炎环境，可导致NK细胞分泌IFN-γ，增加HLA-E表达并通过NKG 2C-HLA-E识别被激活。NK细胞成为适应性或“记忆”细胞，可以通过NKG 2C识别SARS-CoV-2可溶性肽，引发特异性炎症反应以对抗这种病毒。
COVID‐19 disease is the manifestation of syndrome coronavirus 2 (SARS‐CoV‐2) infection, which is causing a worldwide pandemic. This disease can lead to multiple and different symptoms, being lymphopenia associated with severity one of the most persistent. Natural killer cells (NK cells) are part of the innate immune system, being fighting against virus‐infected cells one of their key roles. In this study, we determined the phenotype of NK cells after COVID‐19 and the main characteristic of SARS‐CoV‐2‐specific‐like NK population in the blood of convalescent donors. CD57+ NKG2C+ phenotype in SARS‐CoV‐2 convalescent donors indicates the presence of ‘memory’/activated NK cells as it has been shown for cytomegalovirus infections. Although the existence of this population is donor dependent, its expression may be crucial for the specific response against SARS‐CoV‐2, so that, it gives us a tool for selecting the best donors to produce off‐the‐shelf living drug for cell therapy to treat COVID‐19 patients under the RELEASE clinical trial (NCT04578210). SARS‐CoV‐2 infection induce a pro‐inflammatory environment that could lead to NK cells secreting IFN‐γ, increasing HLA‐E expression and being activated through NKG2C‐HLA‐E recognition. The NK cells become adaptive or “memory” cells that can recognize SARS‐CoV‐2 soluble peptides via NKG2C, triggering a specific inflammatory response to fight this virus.
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