SARS-CoV-2-specific circulating T follicular helper cells correlate with neutralizing antibodies and increase during early convalescence.
SARS-CoV-2-specific circulating T follicular helper cells correlate with neutralizing antibodies and increase during early convalescence.
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DOI：
10.1371/journal.ppat.1009761
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发表时间：
2021-07
期刊：
影响因子：
6.7
通讯作者：
Goepfert PA
中科院分区：
文献类型：
--
作者：
Boppana S;Qin K;Files JK;Russell RM;Stoltz R;Bibollet-Ruche F;Bansal A;Erdmann N;Hahn BH;Goepfert PA
T细胞免疫可能通过帮助产生中和抗体，在预防SARS-CoV-2方面发挥作用。我们在26名恢复期个体中纵向研究了CD4T细胞对SARS-CoV-2 M、N和S结构蛋白的反应。在症状出现后的头两个月内，大多数人(81%)至少获得了一次CD4T细胞应答，48%的人获得了可检测到的SARS-CoV-2特异性循环T滤泡辅助细胞(cTfh，定义为CXCR5+PD1+CD4T细胞)。所有三种蛋白特异性的SARS-CoV-2特异性cTfh反应与抗体中和相关，其中与S蛋白特异性反应的相关性最强。随着时间的推移，随着时间的推移，cTfh反应，特别是对M蛋白的反应，在恢复期增加，第二次恢复期检测到强度超过5%的cTfh反应，中位数为症状出现后38天。症状出现3个月和6个月后，CD4T细胞反应下降，但仍维持在低水平。这些数据加深了我们对SARS-CoV-2感染中抗原特异性cTfh反应的理解，提示在SARS-CoV-2感染中，除S蛋白外，M和N蛋白特异性cTfh也可能有助于中和抗体的产生，cTfh反应的形成可能延迟。自2019年12月以来，冠状病毒病2019(新冠肺炎)大流行在全球范围内造成了显著的发病率和死亡率。最近批准的SARS-CoV-2疫苗被认为是通过诱导中和抗体来预防感染。然而，保护所需的潜在免疫反应仍不清楚。众所周知，T滤泡辅助细胞(TFH)是CD4T细胞的一个亚群，对于中和抗体的产生是必不可少的，其中一些细胞被称为循环T滤泡辅助细胞(CTFH)，可以在血液中进行研究。关于SARS-CoV-2感染中的TFH反应，人们知之甚少。在这里，我们研究了从新冠肺炎中回收的个体对三种主要结构蛋白的cTfh反应。我们发现SARS-CoV-2特异性cTfh频率与中和抗体反应相关。我们还发现，在感染之前，cTfh对SARS-CoV-2的应答在恢复期很好地增加。我们的结果提示，针对其他蛋白的cTfh反应可能有助于中和抗体的产生，并且在SARS-CoV-2感染中cTfh反应的形成可能被延迟。
T-cell immunity is likely to play a role in protection against SARS-CoV-2 by helping generate neutralizing antibodies. We longitudinally studied CD4 T-cell responses to the M, N, and S structural proteins of SARS-CoV-2 in 26 convalescent individuals. Within the first two months following symptom onset, a majority of individuals (81%) mounted at least one CD4 T-cell response, and 48% of individuals mounted detectable SARS-CoV-2-specific circulating T follicular helper cells (cTfh, defined as CXCR5+PD1+ CD4 T cells). SARS-CoV-2-specific cTfh responses across all three protein specificities correlated with antibody neutralization with the strongest correlation observed for S protein-specific responses. When examined over time, cTfh responses, particularly to the M protein, increased in convalescence, and robust cTfh responses with magnitudes greater than 5% were detected at the second convalescent visit, a median of 38 days post-symptom onset. CD4 T-cell responses declined but persisted at low magnitudes three months and six months after symptom onset. These data deepen our understanding of antigen-specific cTfh responses in SARS-CoV-2 infection, suggesting that in addition to S protein, M and N protein-specific cTfh may also assist in the development of neutralizing antibodies and that cTfh response formation may be delayed in SARS-CoV-2 infection. Since December 2019, the Coronavirus Disease 2019 (COVID-19) pandemic has caused significant morbidity and mortality worldwide. Recently approved vaccines against SARS-CoV-2 are understood to protect against infection by inducing neutralizing antibodies. However, the underlying immune responses necessary for protection remain unclear. It is well established that T follicular helper cells (Tfh), a subset of CD4 T cells, are essential to the development of neutralizing antibodies and that some of these cells, called circulating T follicular helper cells (cTfh), can be studied in the blood. Not much is known about Tfh responses mounted in SARS-CoV-2 infection. Here, we studied cTfh responses to three major structural proteins in individuals recovered from COVID-19. We find that SARS-CoV-2-specific cTfh frequencies correlate with neutralizing antibody responses. We also find that cTfh responses to SARS-CoV-2 increase well into convalescence before contracting. Our results suggest that cTfh responses against proteins other than the spike protein may contribute to the development of neutralizing antibodies and that the formation of cTfh responses in SARS-CoV-2 infection may be delayed.
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影响因子：
64.8
作者：
Gaebler C;Wang Z;Lorenzi JCC;Muecksch F;Finkin S;Tokuyama M;Cho A;Jankovic M;Schaefer-Babajew D;Oliveira TY;Cipolla M;Viant C;Barnes CO;Bram Y;Breton G;Hägglöf T;Mendoza P;Hurley A;Turroja M;Gordon K;Millard KG;Ramos V;Schmidt F;Weisblum Y;Jha D;Tankelevich M;Martinez-Delgado G;Yee J;Patel R;Dizon J;Unson-O'Brien C;Shimeliovich I;Robbiani DF;Zhao Z;Gazumyan A;Schwartz RE;Hatziioannou T;Bjorkman PJ;Mehandru S;Bieniasz PD;Caskey M;Nussenzweig MC
通讯作者：
Nussenzweig MC
影响因子：
15.9
作者：
Files, Jacob K.;Boppana, Sushma;Erdmann, Nathan
通讯作者：
Erdmann, Nathan
影响因子：
15.9
作者：
Gong, Fang;Dai, Yaping;Zhou, Pengcheng
通讯作者：
Zhou, Pengcheng
影响因子：
7.8
作者：
George, Parakkal Jovvian;Tai, Wanbo;Lustigman, Sara
通讯作者：
Lustigman, Sara
影响因子：
17.1
作者：
Bentebibel SE;Lopez S;Obermoser G;Schmitt N;Mueller C;Harrod C;Flano E;Mejias A;Albrecht RA;Blankenship D;Xu H;Pascual V;Banchereau J;Garcia-Sastre A;Palucka AK;Ramilo O;Ueno H
通讯作者：
Ueno H