Persistent High Percentage of HLA-DR(+)CD38(high) CD8(+) T Cells Associated With Immune Disorder and Disease Severity of COVID-19.
Persistent High Percentage of HLA-DR(+)CD38(high) CD8(+) T Cells Associated With Immune Disorder and Disease Severity of COVID-19.
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DOI：
10.3389/fimmu.2021.735125
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发表时间：
2021
影响因子：
7.3
通讯作者：
Kong Y
中科院分区：
文献类型：
--
作者：
Du J;Wei L;Li G;Hua M;Sun Y;Wang D;Han K;Yan Y;Song C;Song R;Zhang H;Han J;Liu J;Kong Y
2019冠状病毒病（COVID-19）的全球爆发已演变为全球公共卫生危机，并导致超过1亿例严重病例。进行性淋巴细胞减少，尤其是T细胞减少，是严重COVID-19的一个突出临床特征。活化的HLA-DR+ CD 38 + CD 8 + T细胞从死于埃博拉病毒和流感感染的淋巴细胞减少症患者和感染SARS-CoV-2的重症患者中富集了很长一段时间。然而，据报道，CD 38 +HLA-DR+ CD 8 + T群体在SARS-CoV-2感染中起着相互矛盾的作用。本次回顾性研究共招募了42名在北京地坛医院接受治疗的COVID-19患者，其中包括32名轻度或中度患者和10名重度或危重患者。首先在入院后3天内采集血样，住院期间每3-7天采集一次。在住院期间检查纵向流式细胞术数据。此外，我们使用Luminex多重测定纵向评估了45种细胞因子/趋化因子/生长因子和14种可溶性检查点的血清水平。结果表明，HLA-DR+ CD 38 + CD 8 + T细胞群体具有异质性，可分为两个具有不同特征的亚群：HLA-DR+ CD 38 dim和HLA-DR+ CD 38 hi。我们观察到HLA-DR+ CD 38 hi CD 8 + T细胞在严重的COVID-19患者中持续积累。与HLA-DR + CD 38 dim CD 8 + T细胞相比，这些HLA-DR + CD 38 hi CD 8 + T细胞处于过度活化和随后的失调状态，表现为多个抑制性和刺激性检查点的表达、更高的凋亡敏感性、受损的杀伤潜力和更耗尽的转录调节。此外，临床和实验室数据支持只有HLA-DR+ CD 38 hi CD 8 + T细胞与严重COVID-19患者的全身炎症、组织损伤和免疫紊乱相关。我们的研究结果表明，HLA-DR+ CD 38 hi CD 8 + T细胞与COVID-19的疾病严重程度相关，而不是HLA-DR+ CD 38 dim群体。
The global outbreak of coronavirus disease 2019 (COVID-19) has turned into a worldwide public health crisis and caused more than 100,000,000 severe cases. Progressive lymphopenia, especially in T cells, was a prominent clinical feature of severe COVID-19. Activated HLA-DR+CD38+ CD8+ T cells were enriched over a prolonged period from the lymphopenia patients who died from Ebola and influenza infection and in severe patients infected with SARS-CoV-2. However, the CD38+HLA-DR+ CD8+ T population was reported to play contradictory roles in SARS-CoV-2 infection. A total of 42 COVID-19 patients, including 32 mild or moderate and 10 severe or critical cases, who received care at Beijing Ditan Hospital were recruited into this retrospective study. Blood samples were first collected within 3 days of the hospital admission and once every 3–7 days during hospitalization. The longitudinal flow cytometric data were examined during hospitalization. Moreover, we evaluated serum levels of 45 cytokines/chemokines/growth factors and 14 soluble checkpoints using Luminex multiplex assay longitudinally. We revealed that the HLA-DR+CD38+ CD8+ T population was heterogeneous, and could be divided into two subsets with distinct characteristics: HLA-DR+CD38dim and HLA-DR+CD38hi. We observed a persistent accumulation of HLA-DR+CD38hi CD8+ T cells in severe COVID-19 patients. These HLA-DR+CD38hi CD8+ T cells were in a state of overactivation and consequent dysregulation manifested by expression of multiple inhibitory and stimulatory checkpoints, higher apoptotic sensitivity, impaired killing potential, and more exhausted transcriptional regulation compared to HLA-DR+CD38dim CD8+ T cells. Moreover, the clinical and laboratory data supported that only HLA-DR+CD38hi CD8+ T cells were associated with systemic inflammation, tissue injury, and immune disorders of severe COVID-19 patients. Our findings indicated that HLA-DR+CD38hi CD8+ T cells were correlated with disease severity of COVID-19 rather than HLA-DR+CD38dim population.
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