Format

Send to

Choose Destination
Elife. 2020 Mar 24;9. pii: e52473. doi: 10.7554/eLife.52473.

Rejuvenating conventional dendritic cells and T follicular helper cell formation after vaccination.

Author information

1
Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge, United Kingdom.
2
Epigenetics Programme, Babraham Institute, Cambridge, United Kingdom.
3
Bioceros BV, Utrecht, Netherlands.
4
Division of Nephrology, Department of Medicine and Clinical and Translational Science Institute, University of Rochester Medical Center, Rochester, United States.
5
Autoimmune Genetics Laboratory, VIB and University of Leuven, Leuven, Belgium.
6
Biological Chemistry, Babraham Institute, Cambridge, United Kingdom.
7
Department of Medicine, University of Cambridge, Cambridge, United Kingdom.
#
Contributed equally

Abstract

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.

KEYWORDS:

ageing; dendritic cells; germinal centre response; human; immunology; inflammation; mouse; t follicular helper cells

Supplemental Content

Full text links

Icon for eLife Sciences Publications, Ltd Icon for PubMed Central
Loading ...
Support Center