Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge, United Kingdom.
Epigenetics Programme, Babraham Institute, Cambridge, United Kingdom.
Elife. 2020 Mar 24;9:e52473. doi: 10.7554/eLife.52473.
Germinal centres (GCs) are T follicular helper cell (Tfh)-dependent structures that form in response to vaccination, producing long-lived antibody secreting plasma cells and memory B cells that protect against subsequent infection. With advancing age the GC and Tfh cell response declines, resulting in impaired humoral immunity. We sought to discover what underpins the poor Tfh cell response in ageing and whether it is possible to correct it. Here, we demonstrate that older people and aged mice have impaired Tfh cell differentiation upon vaccination. This deficit is preceded by poor activation of conventional dendritic cells type 2 (cDC2) due to reduced type 1 interferon signalling. Importantly, the Tfh and cDC2 cell response can be boosted in aged mice by treatment with a TLR7 agonist. This demonstrates that age-associated defects in the cDC2 and Tfh cell response are not irreversible and can be enhanced to improve vaccine responses in older individuals.
生发中心（GCs）是滤泡辅助性 T 细胞（Tfh）依赖性结构，它们在接种疫苗后形成，产生长寿命的抗体分泌浆细胞和记忆 B 细胞，以防止随后的感染。随着年龄的增长，GC 和 Tfh 细胞反应下降，导致体液免疫受损。我们试图发现衰老中 Tfh 细胞反应不良的原因，以及是否可以纠正这种情况。在这里，我们证明了老年人和老年小鼠在接种疫苗后 Tfh 细胞分化受损。这种缺陷是由于 1 型干扰素信号减少导致传统树突状细胞 2 型（cDC2）激活不良所致。重要的是，TLR7 激动剂可增强老年小鼠的 Tfh 和 cDC2 细胞反应。这表明 cDC2 和 Tfh 细胞反应的年龄相关缺陷不是不可逆的，可以增强以改善老年人的疫苗反应。
