Impaired HA-specific T follicular helper cell and antibody responses to influenza vaccination are linked to inflammation in humans.
Impaired HA-specific T follicular helper cell and antibody responses to influenza vaccination are linked to inflammation in humans.
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DOI：
10.7554/elife.70554
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发表时间：
2021-11-02
期刊：
影响因子：
7.7
通讯作者：
Linterman MA
中科院分区：
文献类型：
--
作者：
Hill DL;Whyte CE;Innocentin S;Lee JL;Dooley J;Wang J;James EA;Lee JC;Kwok WW;Zand MS;Liston A;Carr EJ;Linterman MA
接种疫苗后产生的抗体可以对流感病毒等病原体随后的感染提供保护性免疫。然而，在接种疫苗后抗体形成受损的情况下，例如在老年人中，要求我们更好地了解成功接种疫苗的细胞和分子机制，以便改进针对高危人群的疫苗设计。在这里，通过研究流感疫苗接种前后抗血凝素(HA)抗体、血清细胞因子以及B和T细胞反应的广度，我们发现循环T滤泡辅助细胞(CTfh)细胞的形成与高滴度抗体反应有关。利用主要组织相容性复合体(MHC)II类四聚体，我们证明了HA特异的cTfh细胞可以来自预先存在的记忆CD4+T细胞，并具有不同的T细胞受体(TCR)谱系。在老年人中，HA特异性细胞向cTfh细胞的分化受到损害。这种cTfh细胞形成的年龄依赖性缺陷不是由于TCR谱系的收缩，而是与cTfh细胞中炎性基因签名的增加有关。总之，这表明在接种疫苗时暂时抑制炎症的策略可能是一种可行的策略，可以在老年人接种疫苗后促进最佳抗体生成。
Antibody production following vaccination can provide protective immunity to subsequent infection by pathogens such as influenza viruses. However, circumstances where antibody formation is impaired after vaccination, such as in older people, require us to better understand the cellular and molecular mechanisms that underpin successful vaccination in order to improve vaccine design for at-risk groups. Here, by studying the breadth of anti-haemagglutinin (HA) IgG, serum cytokines, and B and T cell responses by flow cytometry before and after influenza vaccination, we show that formation of circulating T follicular helper (cTfh) cells was associated with high-titre antibody responses. Using Major Histocompatability Complex (MHC) class II tetramers, we demonstrate that HA-specific cTfh cells can derive from pre-existing memory CD4+ T cells and have a diverse T cell receptor (TCR) repertoire. In older people, the differentiation of HA-specific cells into cTfh cells was impaired. This age-dependent defect in cTfh cell formation was not due to a contraction of the TCR repertoire, but rather was linked with an increased inflammatory gene signature in cTfh cells. Together, this suggests that strategies that temporarily dampen inflammation at the time of vaccination may be a viable strategy to boost optimal antibody generation upon immunisation of older people.