Rejuvenating Conventional Dendritic Cells and T Follicular Helper Cell Formation After Vaccination

Overview

Journal Elife

Specialty Biology

Date 2020 Mar 25

PMID 32204792

Citations 33

Authors

Marisa Stebegg

Alexandre Bignon

Danika Lea Hill

Alyssa Silva-Cayetano

Christel Krueger

Ine Vanderleyden

Silvia Innocentin

Louis Boon

Jiong Wang

Martin S Zand

James Dooley

Jonathan Clark

Adrian Liston

Edward Carr

Michelle A Linterman

Affiliations

Soon will be listed here.

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.

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