Repository logo
 

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

Published version
Peer-reviewed

Type

Article

Change log

Authors

Bignon, Alexandre 
Hill, Danika Lea 
Silva-Cayetano, Alyssa  ORCID logo  https://orcid.org/0000-0003-0533-1629

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.

Description

Keywords

ageing, dendritic cells, germinal centre response, human, immunology, inflammation, mouse, t follicular helper cells, Adolescent, Adoptive Transfer, Adult, Aged, Aging, Animals, B-Lymphocytes, Bone Marrow Cells, CD11 Antigens, Chimera, Female, Germinal Center, Humans, Immunity, Humoral, Immunologic Memory, Influenza Vaccines, Influenza, Human, Male, Mice, Mice, Knockout, Middle Aged, Orthomyxoviridae Infections, Receptor, Interferon alpha-beta, T Follicular Helper Cells, T-Lymphocytes, Helper-Inducer, Vaccination, Young Adult

Journal Title

Elife

Conference Name

Journal ISSN

2050-084X
2050-084X

Volume Title

9

Publisher

eLife Sciences Publications, Ltd