Flavivirus serocomplex cross-reactive immunity is protective by activating heterologous memory CD4 T cells

Wilfried A. A. Saron; Abhay P. S. Rathore; Lim Ting; Eng Eong Ooi; Jenny Low; Soman N. Abraham; Ashley L. St. John

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Flavivirus serocomplex cross-reactive immunity is protective by activating heterologous memory CD4 T cells

机译：黄病毒血清复合物交叉反应性免疫通过激活异源记忆CD4 T细胞而具有保护作用

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How previous immunity influences immune memory recall and protection against related flaviviruses is largely unknown, yet encounter with multiple flaviviruses in a lifetime is increasingly likely. Using sequential challenges with dengue virus (DENV), yellow fever virus (YFV), and Japanese encephalitis virus (JEV), we induced cross-reactive cellular and humoral immunity among flaviviruses from differing serocomplexes. Antibodies against JEV enhanced DENV replication; however, JEV immunity was protective in vivo during secondary DENV1 infection, promoting rapid gains in antibody avidity. Mechanistically, JEV immunity activated dendritic cells and effector memory T cells, which developed a T follicular helper cell phenotype in draining lymph nodes upon secondary DENV1 infection. We identified cross-reactive epitopes that promote recall from a pool of flavivirus serocomplex cross-reactive memory CD4 T cells and confirmed that a similar serocomplex cross-reactive immunity occurs in humans. These results show that sequential immunizations for flaviviruses sharing CD4 epitopes should promote protection during a subsequent heterologous infection.

机译：先前的免疫如何影响免疫记忆的回忆和对相关黄病毒的保护在很大程度上是未知的，但是在一生中与多种黄病毒的接触越来越有可能。使用登革热病毒（DENV），黄热病病毒（YFV）和日本脑炎病毒（JEV）的顺序攻击，我们诱导了来自不同血清复合物的黄病毒之间的交叉反应性细胞和体液免疫。针对JEV的抗体可增强DENV复制;然而，JEV免疫在继发DENV1感染期间在体内具有保护作用，从而促进抗体亲和力的快速获得。从机制上讲，JEV免疫激活了树突状细胞和效应记忆T细胞，继发DENV1感染后，它们在引流淋巴结中形成了T滤泡辅助细胞表型。我们确定了交叉反应性抗原决定簇，可促进从黄病毒血清复合物交叉反应性记忆CD4 T细胞池中召回，并确认相似的血清复合物交叉反应性免疫力会在人类中发生。这些结果表明，针对共享CD4表位的黄病毒的顺序免疫应在随后的异源感染中促进保护。

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《Science Advances》 |2018年第7期|共页
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Wilfried A. A. Saron; Abhay P. S. Rathore; Lim Ting; Eng Eong Ooi; Jenny Low; Soman N. Abraham; Ashley L. St. John;
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1. Cross-Reactive Memory CD4+ T Cells Alter the CD8+ T-Cell Response to Heterologous Secondary Dengue Virus Infections in Mice in a Sequence-Specific Manner [J] . Coreen M. Beaumier, Alan L. Rothman Viral Immunology . 2009,第3期

机译：交叉反应性记忆CD4 + T细胞以特定于序列的方式改变小鼠对异源继发登革热病毒感染的CD8 + T细胞反应。
2. Cross-reactive memory CD4+ T cells alter the CD8+ T-cell response to heterologous secondary dengue virus infections in mice in a sequence-specific manner. [J] . Beaumier CM, Rothman AL Viral immunology . 2009,第3期

机译：交叉反应性记忆CD4 + T细胞以序列特异性方式改变了小鼠对异源继发登革热病毒感染的CD8 + T细胞反应。
3. Disparate Epitopes Mediating Protective Heterologous Immunity to Unrelated Viruses Share Peptide–MHC Structural Features Recognized by Cross-Reactive T Cells [J] . Zu T. Shen, Tina T. Nguyen, Keith A. Daniels, The journal of immunology . 2013,第10期

机译：介导无关病毒的保护性异源免疫的不同表位共享交叉反应性T细胞识别的肽-MHC结构特征
4. CD40-ACTIVATED B (CD40-B) CELLS LOADED WITH AUTOLOGOUS TUMOR RNA AS A NOVEL ANTIGEN-PRESENTING CELL VACCINE FOR CANINE LYMPHOMA [C] . Amy LaBlanc, Erika L Krick, Beth Overley, Annual conference of the Veterinary Cancer Society . 2008

机译：CD40-活化的B（CD40-B）用自体肿瘤RNA负载，作为犬淋巴瘤的新型抗原呈递细胞疫苗
5. The role of CD4+ T cell help and the co-stimulatory molecule CD40 in protective immunity against liver stage Plasmodium infection [D] . Murray, Sara 2013

机译：CD4 + T细胞帮助和共刺激分子CD40在针对肝脏阶段性疟原虫感染的保护性免疫中的作用
6. Flavivirus serocomplex cross-reactive immunity is protective by activating heterologous memory CD4 T cells [O] . Wilfried A. A. Saron, Abhay P. S. Rathore, Lim Ting, 2018

机译：黄病毒血清复合物交叉反应性免疫通过激活异源记忆CD4 T细胞而具有保护作用
7. Cross-Reactive Memory CD4+ T Cells Alter the CD8+ T-Cell Response to Heterologous Secondary Dengue Virus Infections in Mice in a Sequence-Specific Manner [O] . Beaumier, Coreen M., Rothman, Alan L. 2009

机译：交叉反应性记忆CD4 + T细胞以特定于序列的方式改变小鼠对异源继发登革热病毒感染的CD8 + T细胞反应。

Flavivirus serocomplex cross-reactive immunity is protective by activating heterologous memory CD4 T cells

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