Deficiency of Tfh Cells and Germinal Center in Deceased COVID-19 Patients

被引:44
作者
Duan, Ya-qi [1 ,2 ]
Xia, Ming-hui [3 ]
Ren, Liang [4 ]
Zhang, Yan-fang [5 ]
Ao, Qi-lin [1 ,2 ]
Xu, San-peng [1 ]
Kuang, Dong [1 ]
Liu, Qian [4 ]
Yan, Bing [5 ]
Zhou, Yi-wu [4 ]
Chu, Qian [6 ]
Liu, Liang [4 ]
Yang, Xiang-Ping [3 ]
Wang, Guo-ping [1 ,2 ]
机构
[1] Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Inst Pathol, Wuhan 430030, Peoples R China
[2] Huazhong Univ Sci & Technol, Tongji Med Coll, Sch Basic Med, Dept Pathol, Wuhan 430030, Peoples R China
[3] Huazhong Univ Sci & Technol, Tongji Med Coll, Sch Basic Med, Dept Immunol, Wuhan 430030, Peoples R China
[4] Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Forens Med, Wuhan 430030, Peoples R China
[5] Chinese Acad Sci, Ctr Biosafety Megasci, Wuhan Inst Virol, State Key Lab Virol, Wuhan 430071, Peoples R China
[6] Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Oncol, Wuhan 430030, Peoples R China
关键词
COVID-19; immune responses; germinal center; T follicular helper cells;
D O I
10.1007/s11596-020-2225-x
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
The COVID-19 pandemic caused by SARS-CoV2 is characterized by a remarkable variation in clinical severity ranging from a mild illness to a fatal multi-organ disease. Understanding the dysregulated human immune responses in the fatal subjects is critical for management of COVID-19 patients and the pandemic. In this study, we examined the immune cell compositions in the lung tissues and hilar lymph nodes using immunohistochemistry on 6 deceased COVID-19 patients and 4 focal organizing pneumonia (FOP) patients who underwent lung surgery and served as controls. We found a dominant presence of macrophages and a general deficiency of T cells and B cells in the lung tissues from deceased COVID-19 patients. In contrast to the FOP patients, Tfh cells and germinal center formation were largely absent in the draining hilar lymph nodes in the deceased COVID-19 patients. This was correlated with reduced IgM and IgG levels compared to convalescent COVID-19 patients. In summary, our data highlight a defect of germinal center structure in deceased COVID-19 patients leading to an impaired humoral immunity. Understanding the mechanisms of this deficiency will be one of the key points for the management of this epidemic.
引用
收藏
页码:618 / 624
页数:7
相关论文
共 19 条
[1]   Potent Neutralizing Antibodies against SARS-CoV-2 Identified by High-Throughput Single-Cell Sequencing of Convalescent Patients' B Cells [J].
Cao, Yunlong ;
Su, Bin ;
Guo, Xianghua ;
Sun, Wenjie ;
Deng, Yongqiang ;
Bao, Linlin ;
Zhu, Qinyu ;
Zhang, Xu ;
Zheng, Yinghui ;
Geng, Chenyang ;
Chai, Xiaoran ;
He, Runsheng ;
Li, Xiaofeng ;
Lv, Qi ;
Zhu, Hua ;
Deng, Wei ;
Xu, Yanfeng ;
Wang, Yanjun ;
Qiao, Luxin ;
Tan, Yafang ;
Song, Liyang ;
Wang, Guopeng ;
Du, Xiaoxia ;
Gao, Ning ;
Liu, Jiangning ;
Xiao, Junyu ;
Su, Xiao-dong ;
Du, Zongmin ;
Feng, Yingmei ;
Qin, Chuan ;
Qin, Chengfeng ;
Jin, Ronghua ;
Xie, X. Sunney .
CELL, 2020, 182 (01) :73-+
[2]   Clinical and immunological features of severe and moderate coronavirus disease 2019 [J].
Chen, Guang ;
Wu, Di ;
Guo, Wei ;
Cao, Yong ;
Huang, Da ;
Wang, Hongwu ;
Wang, Tao ;
Zhang, Xiaoyun ;
Chen, Huilong ;
Yu, Haijing ;
Zhang, Xiaoping ;
Zhang, Minxia ;
Wu, Shiji ;
Song, Jianxin ;
Chen, Tao ;
Han, Meifang ;
Li, Shusheng ;
Luo, Xiaoping ;
Zhao, Jianping ;
Ning, Qin .
JOURNAL OF CLINICAL INVESTIGATION, 2020, 130 (05) :2620-2629
[3]   Follicular Helper CD4 T Cells (TFH) [J].
Crotty, Shane .
ANNUAL REVIEW OF IMMUNOLOGY, VOL 29, 2011, 29 :621-663
[4]   B Cell Responses: Cell Interaction Dynamics and Decisions [J].
Cyster, Jason G. ;
Allen, Christopher D. C. .
CELL, 2019, 177 (03) :524-540
[5]   Reduction and Functional Exhaustion of T Cells in Patients With Coronavirus Disease 2019 (COVID-19) [J].
Diao, Bo ;
Wang, Chenhui ;
Tan, Yingjun ;
Chen, Xiewan ;
Liu, Ying ;
Ning, Lifen ;
Chen, Li ;
Li, Min ;
Liu, Yueping ;
Wang, Gang ;
Yuan, Zilin ;
Feng, Zeqing ;
Zhang, Yi ;
Wu, Yuzhang ;
Chen, Yongwen .
FRONTIERS IN IMMUNOLOGY, 2020, 11
[6]   Complex Immune Dysregulation in COVID-19 Patients with Severe Respiratory Failure [J].
Giamarellos-Bourboulis, Evangelos J. ;
Netea, Mihai G. ;
Rovina, Nikoletta ;
Akinosoglou, Karolina ;
Antoniadou, Anastasia ;
Antonakos, Nikolaos ;
Damoraki, Georgia ;
Gkavogianni, Theologia ;
Adami, Maria-Evangelia ;
Katsaounou, Paraskevi ;
Ntaganou, Maria ;
Kyriakopoulou, Magdalini ;
Dimopoulos, George ;
Koutsodimitropoulos, Ioannis ;
Velissaris, Dimitrios ;
Koufargyris, Panagiotis ;
Karageorgos, Athanassios ;
Katrini, Konstantina ;
Lekakis, Vasileios ;
Lupse, Mihaela ;
Kotsaki, Antigone ;
Renieris, George ;
Theodoulou, Danai ;
Panou, Vassiliki ;
Koukaki, Evangelia ;
Koulouris, Nikolaos ;
Gogos, Charalambos ;
Koutsoukou, Antonia .
CELL HOST & MICROBE, 2020, 27 (06) :992-+
[7]   Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals [J].
Grifoni, Alba ;
Weiskopf, Daniela ;
Ramirez, Sydney, I ;
Mateus, Jose ;
Dan, Jennifer M. ;
Moderbacher, Carolyn Rydyznski ;
Rawlings, Stephen A. ;
Sutherland, Aaron ;
Premkumar, Lakshmanane ;
Jadi, Ramesh S. ;
Marrama, Daniel ;
de Silva, Aravinda M. ;
Frazier, April ;
Carlin, Aaron F. ;
Greenbaum, Jason A. ;
Peters, Bjoern ;
Krammer, Florian ;
Smith, Davey M. ;
Crotty, Shane ;
Sette, Alessandro .
CELL, 2020, 181 (07) :1489-+
[8]   Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China (vol 395, pg 497, 2020) [J].
Huang, C. ;
Wang, Y. ;
Li, X. .
LANCET, 2020, 395 (10223) :496-496
[9]   Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus [J].
Li, WH ;
Moore, MJ ;
Vasilieva, N ;
Sui, JH ;
Wong, SK ;
Berne, MA ;
Somasundaran, M ;
Sullivan, JL ;
Luzuriaga, K ;
Greenough, TC ;
Choe, H ;
Farzan, M .
NATURE, 2003, 426 (6965) :450-454
[10]   Germinal Center B Cell Dynamics [J].
Mesin, Luka ;
Ersching, Jonatan ;
Victora, Gabriel D. .
IMMUNITY, 2016, 45 (03) :471-482