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

eLife (2020-03-25)
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
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.

MATERIALS
Product Number
Brand
Product Description

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Triton X-100, laboratory grade
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Sucrose, for molecular biology, ≥99.5% (GC)
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Fetal Bovine Serum, Heat Inactivated, non-USA origin, sterile-filtered, suitable for cell culture
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Albumin from chicken egg white, lyophilized powder, ≥98% (agarose gel electrophoresis)
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Paraformaldehyde, reagent grade, crystalline
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Sodium phosphate, 96%
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Freund′s Adjuvant, Incomplete, liquid
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L-Lysine, ≥98% (TLC)
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Streptavidin from Streptomyces avidinii, essentially salt-free, lyophilized powder, ≥13 units/mg protein
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Pertussis toxin from Bordetella pertussis, lyophilized powder
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Lysozyme from chicken egg white, dialyzed, lyophilized, powder, ~100000 U/mg
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N-Acetyl-D-lactosamine, ≥98%