Profound dysregulation of T cell homeostasis and function in patients with severe COVID-19.
Profound dysregulation of T cell homeostasis and function in patients with severe COVID-19.
复制标题
重症新冠肺炎患者T细胞平衡和功能严重失调。
作者：
Adamo S;Chevrier S;Cervia C;Zurbuchen Y;Raeber ME;Yang L;Sivapatham S;Jacobs A;Baechli E;Rudiger A;Stüssi-Helbling M;Huber LC;Schaer DJ;Bodenmiller B;Boyman O;Nilsson J
2019年冠状病毒病（COVID-19）是由严重急性呼吸道综合征冠状病毒2（SARS-CoV-2）感染引起的，表现出从无症状感染到致命疾病的广泛临床表现。与严重COVID-19相关的一个非常突出的特征是T细胞淋巴细胞减少症。然而，T细胞的稳态和功能特性在COVID-19中并不明确。我们前瞻性地将轻度和重度COVID-19患者纳入我们的多中心队列，并使用40参数质谱仪、流式细胞术、靶向蛋白质组学和功能测定对T细胞的表型和功能特征进行了横断面分析。与轻度疾病相比，我们观察到严重COVID-19患者外周T细胞稳态和功能的强烈扰动。患有严重COVID-19的个体表现出T细胞淋巴细胞减少症和T细胞群的重新分布，包括幼稚T细胞的损失，向CD 4 +T滤泡辅助细胞和细胞毒性CD 4 + T细胞倾斜，以及活化和耗尽的T细胞的扩增。广泛的T细胞凋亡是特别明显的严重疾病和T细胞淋巴细胞减少症，这反过来又伴随着受损的T细胞对几种常见的病毒抗原的反应。患有严重疾病的患者显示白细胞介素-7升高和T细胞增殖增加。此外，在症状发作后较晚时间点采样的患者具有较高的T细胞计数和改善的抗病毒T细胞应答。我们的研究表明，严重的COVID-19的特征是广泛的T细胞功能障碍和T细胞凋亡，这与稳态T细胞增殖和T细胞恢复的迹象有关。在严重的COVID-19中，T细胞群显示出扰动，包括幼稚T细胞的损失，CD 4 + T细胞向T滤泡辅助细胞和细胞毒性表型倾斜，以及活化和耗尽的T细胞的扩增。细胞凋亡和迁移导致严重疾病的淋巴细胞减少症，伴有白细胞介素7升高。在严重的COVID-19中，对病毒抗原的功能反应降低。缩略语：COVID-19，2019年冠状病毒病; CyTOF，飞行时间流式细胞术; TFH，T滤泡辅助细胞
Coronavirus disease 2019 (COVID‐19) is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and shows a broad clinical presentation ranging from asymptomatic infection to fatal disease. A very prominent feature associated with severe COVID‐19 is T cell lymphopenia. However, homeostatic and functional properties of T cells are ill‐defined in COVID‐19. We prospectively enrolled individuals with mild and severe COVID‐19 into our multicenter cohort and performed a cross‐sectional analysis of phenotypic and functional characteristics of T cells using 40‐parameter mass cytometry, flow cytometry, targeted proteomics, and functional assays. Compared with mild disease, we observed strong perturbations of peripheral T cell homeostasis and function in severe COVID‐19. Individuals with severe COVID‐19 showed T cell lymphopenia and redistribution of T cell populations, including loss of naïve T cells, skewing toward CD4+T follicular helper cells and cytotoxic CD4+ T cells, and expansion of activated and exhausted T cells. Extensive T cell apoptosis was particularly evident with severe disease and T cell lymphopenia, which in turn was accompanied by impaired T cell responses to several common viral antigens. Patients with severe disease showed elevated interleukin‐7 and increased T cell proliferation. Furthermore, patients sampled at late time points after symptom onset had higher T cell counts and improved antiviral T cell responses. Our study suggests that severe COVID‐19 is characterized by extensive T cell dysfunction and T cell apoptosis, which is associated with signs of homeostatic T cell proliferation and T cell recovery. In severe COVID‐19 T cell populations show perturbations, including loss of naïve T cells, CD4+ T cell skewing toward T follicular helper and cytotoxic phenotypes and expansion of activated and exhausted T cells. Apoptosis and migration contribute to the lymphopenia of severe disease, which is accompanied by Interleukin‐7 elevation. Functional responses to viral antigens are reduced in severe COVID‐19. Abbreviations: COVID‐19, coronavirus disease 2019; CyTOF, cytometry by time‐of‐flight; TFH, T follicular helper cell
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影响因子：
64.5
作者：
Levine JH;Simonds EF;Bendall SC;Davis KL;Amir el-AD;Tadmor MD;Litvin O;Fienberg HG;Jager A;Zunder ER;Finck R;Gedman AL;Radtke I;Downing JR;Pe'er D;Nolan GP
通讯作者：
Nolan GP
影响因子：
5.4
作者：
Fadell, Shaza A.;Bromley, Shannon K.;Medoff, Benjamin D.;Luster, Andrew D.
通讯作者：
Luster, Andrew D.
DOI：
10.1164/rccm.202002-0445oc
发表时间：
2020-06-01
影响因子：
24.7
作者：
Feng, Yun;Ling, Yun;Qu, Jieming
通讯作者：
Qu, Jieming
影响因子：
30.5
作者：
Kaech, SM;Tan, JT;Ahmed, R
通讯作者：
Ahmed, R
影响因子：
17.1
作者：
Karakus, Ufuk;Sahin, Dilara;Boyman, Onur
通讯作者：
Boyman, Onur