CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
University of Chinese Academy of Sciences, Beijing, China.
Nat Commun. 2019 Aug 27;10(1):3859. doi: 10.1038/s41467-019-11754-0.
Induction of long-lived antibody responses during infection or vaccination is often essential for subsequent protection, but the relative contributions of T follicular helper (Tfh) cells and T helper 1 (Th1) cells for induction of antigen specific antibody responses to viruses are unclear. Here, we establish an acute Zika virus (ZIKV) infection model in immunocompetent mice, and show that ZIKV infection elicits robust Th1-like Tfh cell and protective antibody responses. While these Th1-like Tfh cells share phenotypic and transcriptomic profiles with both Tfh and Th1 cells, they also have unique surface markers and gene expression characteristics, and are dependent on T-bet for their development. Th1-like Tfh cells, but not Th1 cells, are essential for class switching of ZIKV-specific IgG2c antibodies and maintenance of long-term neutralizing antibody responses. Our study suggests that specific modulation of the Th1-like Tfh cell response during infection or vaccination may augment the induction of antiviral antibody response to ZIKV and other viruses.
在感染或接种疫苗期间诱导长期的抗体反应通常对于随后的保护至关重要，但 T 滤泡辅助（Tfh）细胞和 T 辅助 1（Th1）细胞对诱导针对病毒的抗原特异性抗体反应的相对贡献尚不清楚。在这里，我们建立了免疫功能正常的小鼠的急性寨卡病毒（ZIKV）感染模型，并表明 ZIKV 感染会引发强烈的 Th1 样 Tfh 细胞和保护性抗体反应。虽然这些 Th1 样 Tfh 细胞与 Tfh 和 Th1 细胞具有相似的表型和转录组特征，但它们也具有独特的表面标志物和基因表达特征，并且其发育依赖于 T-bet。Th1 样 Tfh 细胞而非 Th1 细胞对于 ZIKV 特异性 IgG2c 抗体的类别转换和长期中和抗体反应的维持至关重要。我们的研究表明，在感染或接种疫苗期间对 Th1 样 Tfh 细胞反应的特定调节可能会增强对 ZIKV 和其他病毒的抗病毒抗体反应的诱导。
