Huber Johanna E, Ahlfeld Julia, Scheck Magdalena K, Zaucha Magdalena, Witter Klaus, Lehmann Lisa, Karimzadeh Hadi, Pritsch Michael, Hoelscher Michael, von Sonnenburg Frank, Dick Andrea, Barba-Spaeth Giovanna, Krug Anne B, Rothenfußer Simon, Baumjohann Dirk
Institute for Immunology Biomedical Center Faculty of Medicine LMU Munich Planegg-Martinsried Germany.
Division of Clinical Pharmacology University Hospital LMU Munich Munich Germany.
Clin Transl Immunology. 2020 May 13;9(5):e1129. doi: 10.1002/cti2.1129. eCollection 2020 May.
T follicular helper (Tfh) cells are the principal T helper cell subset that provides help to B cells for potent antibody responses against various pathogens. In this study, we took advantage of the live-attenuated yellow fever virus (YFV) vaccine strain, YF-17D, as a model system for studying human antiviral immune responses following exposure to an acute primary virus challenge under safe and highly controlled conditions, to comprehensively analyse the dynamics of circulating Tfh (cTfh) cells.
We tracked and analysed the response of cTfh and other T and B cell subsets in peripheral blood of healthy volunteers by flow cytometry over the course of 4 weeks after YF-17D vaccination.
Using surface staining of cell activation markers to track YFV-specific T cells, we found increasing cTfh cell frequencies starting at day 3 and peaking around 2 weeks after YF-17D vaccination. This kinetic was confirmed in a subgroup of donors using MHC multimer staining for four known MHC class II epitopes of YF-17D. The subset composition of cTfh cells changed dynamically during the course of the immune response and was dominated by the cTfh1-polarised subpopulation. Importantly, frequencies of cTfh1 cells correlated with the strength of the neutralising antibody response, whereas frequencies of cTfh17 cells were inversely correlated.
In summary, we describe detailed cTfh kinetics during YF-17D vaccination. Our results suggest that cTfh expansion and polarisation can serve as a prognostic marker for vaccine success. These insights may be leveraged in the future to improve current vaccine design and strategies.
滤泡辅助性T细胞（Tfh）是主要的辅助性T细胞亚群，可帮助B细胞针对各种病原体产生有效的抗体反应。在本研究中，我们利用减毒活黄热病毒（YFV）疫苗株YF-17D作为模型系统，在安全且高度可控的条件下研究人类在暴露于急性原发性病毒攻击后的抗病毒免疫反应，以全面分析循环Tfh（cTfh）细胞的动态变化。
我们通过流式细胞术追踪并分析了健康志愿者在接种YF-17D疫苗后4周内外周血中cTfh及其他T和B细胞亚群的反应。
通过细胞活化标志物的表面染色来追踪YFV特异性T细胞，我们发现cTfh细胞频率从第3天开始增加，并在接种YF-17D疫苗后约2周达到峰值。使用针对YF-17D的四个已知MHC II类表位的MHC多聚体染色，在一部分供体中证实了这种动力学变化。cTfh细胞的亚群组成在免疫反应过程中动态变化，并且以cTfh1极化亚群为主。重要的是，cTfh1细胞的频率与中和抗体反应的强度相关，而cTfh17细胞的频率则呈负相关。
总之，我们描述了接种YF-17D疫苗期间详细的cTfh动力学变化。我们的结果表明，cTfh的扩增和极化可作为疫苗成功的预后标志物。这些见解未来可能会被用于改进当前的疫苗设计和策略。
