Low-Avidity CD4(+) T Cell Responses to SARS-CoV-2 in Unexposed Individuals and Humans with Severe COVID-19.
Low-Avidity CD4(+) T Cell Responses to SARS-CoV-2 in Unexposed Individuals and Humans with Severe COVID-19.
复制标题
DOI：
10.1016/j.immuni.2020.11.016
复制
发表时间：
2020-12-15
期刊：
影响因子：
32.4
通讯作者：
Scheffold A
中科院分区：
文献类型：
--
作者：
Bacher P;Rosati E;Esser D;Martini GR;Saggau C;Schiminsky E;Dargvainiene J;Schröder I;Wieters I;Khodamoradi Y;Eberhardt F;Vehreschild MJGT;Neb H;Sonntagbauer M;Conrad C;Tran F;Rosenstiel P;Markewitz R;Wandinger KP;Augustin M;Rybniker J;Kochanek M;Leypoldt F;Cornely OA;Koehler P;Franke A;Scheffold A
在未接触SARS-CoV-2的个体中可以发现对SARS-CoV-2有反应的CD4+T细胞，这些细胞被认为是对普通感冒冠状病毒(CCCoV)感染的反应。在这里，我们利用SARS-CoV-2反应性CD4+T细胞的浓缩来检测这些细胞的抗原亲和力和克隆性，以及CCCoV交叉反应的相对贡献。几乎所有接受检查的未暴露者中都存在SARS-CoV-2反应性CD4+记忆T细胞，表现出低功能亲和力和多种高度可变的交叉反应，这些反应并不局限于CCCoV。来自新冠肺炎患者的反应性CD+T细胞对CCCoV缺乏交叉反应，无论在所有被分析的捐赠者中对CCCoV有强烈的记忆T细胞反应。在重度但不轻微的新冠肺炎中，SARS-CoV-2特异性T细胞显示出低功能亲和力和克隆性，尽管频率增加。我们的发现将低亲和力的CD_4+T细胞反应确定为严重新冠肺炎的特征，并反对CCCoV反应性T细胞在SARS-CoV-2感染中的保护作用。Bacher等人。将T细胞对SARS-CoV-2过度但低亲和力的反应确定为严重但不轻微的新冠肺炎的标志。未暴露的捐赠者对SARS-CoV-2的先前记忆也表现出低亲和力，并包含多种高度可变的交叉反应，这些反应并不局限于普通感冒冠状病毒。
CD4+ T cells reactive against SARS-CoV-2 can be found in unexposed individuals, and these are suggested to arise in response to common cold coronavirus (CCCoV) infection. Here, we utilized SARS-CoV-2-reactive CD4+ T cell enrichment to examine the antigen avidity and clonality of these cells, as well as the relative contribution of CCCoV cross-reactivity. SARS-CoV-2-reactive CD4+ memory T cells were present in virtually all unexposed individuals examined, displaying low functional avidity and multiple, highly variable cross-reactivities that were not restricted to CCCoVs. SARS-CoV-2-reactive CD4+ T cells from COVID-19 patients lacked cross-reactivity to CCCoVs, irrespective of strong memory T cell responses against CCCoV in all donors analyzed. In severe but not mild COVID-19, SARS-CoV-2-specific T cells displayed low functional avidity and clonality, despite increased frequencies. Our findings identify low-avidity CD4+ T cell responses as a hallmark of severe COVID-19 and argue against a protective role for CCCoV-reactive T cells in SARS-CoV-2 infection. Bacher et al. identify excessive but low-avidity T cell responses to SARS-CoV-2 as a hallmark of severe but not mild COVID-19. Pre-existing memory to SARS-CoV-2 in unexposed donors also displayed low avidity and harbored multiple, highly variable cross-reactivities that were not restricted to common cold coronaviruses.
登录
查看更多内容
影响因子：
64.5
作者：
Birnbaum ME;Mendoza JL;Sethi DK;Dong S;Glanville J;Dobbins J;Ozkan E;Davis MM;Wucherpfennig KW;Garcia KC
通讯作者：
Garcia KC
DOI：
10.1186/s12979-018-0122-y
发表时间：
2018
期刊：
Immunity & ageing : I & A
影响因子：
--
作者：
Lanzer KG;Cookenham T;Reiley WW;Blackman MA
通讯作者：
Blackman MA
影响因子：
168.9
作者：
Huang, Chaolin;Wang, Yeming;Cao, Bin
通讯作者：
Cao, Bin
影响因子：
4
作者：
Bacher, Petra;Scheffold, Alexander
通讯作者：
Scheffold, Alexander
影响因子：
100.3
作者：
Chen, Zeyu;John Wherry, E.
通讯作者：
John Wherry, E.