COVID-19 immune signatures reveal stable antiviral T cell function despite declining humoral responses.
COVID-19 immune signatures reveal stable antiviral T cell function despite declining humoral responses.
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DOI：
10.1016/j.immuni.2021.01.008
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发表时间：
2021-02-09
期刊：
影响因子：
32.4
通讯作者：
Eiz-Vesper B
中科院分区：
文献类型：
--
作者：
Bonifacius A;Tischer-Zimmermann S;Dragon AC;Gussarow D;Vogel A;Krettek U;Gödecke N;Yilmaz M;Kraft ARM;Hoeper MM;Pink I;Schmidt JJ;Li Y;Welte T;Maecker-Kolhoff B;Martens J;Berger MM;Lobenwein C;Stankov MV;Cornberg M;David S;Behrens GMN;Witzke O;Blasczyk R;Eiz-Vesper B
对SARS-CoV-2的细胞和体液免疫对于控制原发感染至关重要，并与疾病的严重程度相关。SARS-CoV-2特异性T细胞免疫的作用，其与抗体的关系，以及针对地方性冠状病毒（huCoV）的预先存在的免疫力（假设具有保护作用），在82名健康供体（HD），204名康复者（RC）和92名活动性COVID-19患者（AC）中进行了研究。AC具有高量的抗SARS-CoV-2核衣壳和刺突IgG，但由于炎性环境、抑制性分子（PD-1、Tim-3）的表达以及T细胞中的效应物半胱天冬酶-3、-7和-8活性，淋巴细胞减少和总体降低的抗病毒T细胞应答。SARS-CoV-2特异性T细胞免疫由多功能的、主要分泌干扰素-γ的CD 4 + T细胞赋予，在整个恢复期保持稳定，而体液应答下降。对huCoV的免疫反应在RC与轻度疾病和强细胞SARS-CoV-2 T细胞反应性暗示了对huCoV的预先存在的免疫保护作用。COVID-19从无症状感染到多器官衰竭各不相同，但缺乏疾病期间及之后针对SARS-CoV-2的细胞免疫数据。Bonifacius等人显示出疾病期间对地方性冠状病毒的预先存在的免疫力和在恢复期间早期伴随体液应答降低的稳定的细胞免疫力的有益效果。
Cellular and humoral immunity to SARS-CoV-2 is critical to control primary infection and correlates with severity of disease. The role of SARS-CoV-2-specific T cell immunity, its relationship to antibodies, and pre-existing immunity against endemic coronaviruses (huCoV), which has been hypothesized to be protective, were investigated in 82 healthy donors (HDs), 204 recovered (RCs), and 92 active COVID-19 patients (ACs). ACs had high amounts of anti-SARS-CoV-2 nucleocapsid and spike IgG but lymphopenia and overall reduced antiviral T cell responses due to the inflammatory milieu, expression of inhibitory molecules (PD-1, Tim-3) as well as effector caspase-3, -7, and -8 activity in T cells. SARS-CoV-2-specific T cell immunity conferred by polyfunctional, mainly interferon-γ-secreting CD4+ T cells remained stable throughout convalescence, whereas humoral responses declined. Immune responses toward huCoV in RCs with mild disease and strong cellular SARS-CoV-2 T cell reactivity imply a protective role of pre-existing immunity against huCoV. COVID-19 varies from asymptomatic infection to multiorgan failure, but data on cellular immunity against SARS-CoV-2 during disease and beyond are lacking. Bonifacius et al. show a beneficial effect of preexisting immunity to endemic coronaviruses during disease and stable cellular immunity with concomitant decrease of humoral responses early during convalescence.
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