Relationship of SARS-CoV-2-specific CD4 response to COVID-19 severity and impact of HIV-1 and tuberculosis coinfection
Relationship of SARS-CoV-2-specific CD4 response to COVID-19 severity and impact of HIV-1 and tuberculosis coinfection
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DOI：
10.1172/jci149125
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发表时间：
2021-06-15
影响因子：
15.9
通讯作者：
Wilkinson, Robert J.
中科院分区：
文献类型：
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作者：
Riou, Catherine;du Bruyn, Elsa;Wilkinson, Robert J.
T 细胞参与 2019 年冠状病毒病 (COVID-19) 的控制，但对抗原特异性 T 细胞反应与疾病严重程度之间关系的了解有限。在这里，我们使用流式细胞术评估了 95 名住院 COVID-19 患者（其中 38 名同时感染 HIV-1 和/或结核病 (TB)）和 38 名非 COVID-19 患者中 SARS 冠状病毒 2 特异性（SARS-CoV-2 特异性）CD4(+) T 细胞的数量、功能和表型。我们发现，SARS-CoV-2 特异性 CD4(+) T 细胞属性（而不是数量）与疾病严重程度相关，严重疾病的特点是多功能潜力差、增殖能力降低和 HLA-DR 表达增强。此外，HIV-1 和结核病同时感染会扭曲 SARS-CoV-2 T 细胞反应。在患有活动性结核病的 COVID-19 患者中观察到 HIV-1 介导的 CD4(+) T 细胞耗竭与 T 细胞和对 SARS-CoV-2 的体液免疫反应欠佳相关，并且 SARS-CoV-2 特异性 CD4(+) T 细胞的多功能能力下降。我们的结果还显示，COVID-19 患者的结核分枝杆菌特异性 CD4(+) T 细胞频率降低，这可能对结核病进展产生影响。这些结果证实了 SARS-CoV-2 特异性 T 细胞在 COVID-19 发病机制中的重要作用，并支持重症患者 T 细胞功能改变的概念。
T cells are involved in control of coronavirus disease 2019 (COVID-19), but limited knowledge is available on the relationship between antigen-specific T cell response and disease severity. Here, we used flow cytometry to assess the magnitude, function, and phenotype of SARS coronavirus 2-specific (SARS-CoV-2-specific) CD4(+) T cells in 95 hospitalized COVID-19 patients, 38 of them being HIV-1 and/or tuberculosis (TB) coinfected, and 38 non-COVID-19 patients. We showed that SARS-CoV-2-specific CD4(+) T cell attributes, rather than magnitude, were associated with disease severity, with severe disease being characterized by poor polyfunctional potential, reduced proliferation capacity, and enhanced HLA-DR expression. Moreover, HIV-1 and TB coinfection skewed the SARS-CoV-2 T cell response. HIV-1-mediated CD4(+) T cell depletion associated with suboptimal T cell and humoral immune responses to SARS-CoV-2, and a decrease in the polyfunctional capacity of SARS-CoV-2-specific CD4(+) T cells was observed in COVID-19 patients with active TB. Our results also revealed that COVID-19 patients displayed reduced frequency of Mycobacterium tuberculosis-specific CD4(+) T cells, with possible implications for TB disease progression. These results corroborate the important role of SARS-CoV-2-specific T cells in COVID-19 pathogenesis and support the concept of altered T cell functions in patients with severe disease.