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Antigen presentation kinetics control T cell/dendritic cell interactions and follicular helper T cell generation in vivo


Benson, R A; MacLeod, M KL; Hale, B G; Patakas, A; Garside, P; Brewer, J M (2015). Antigen presentation kinetics control T cell/dendritic cell interactions and follicular helper T cell generation in vivo. eLife, 4:e06994.

Abstract

The production of high affinity, class switched antibodies produced by B cells hinges on the effective differentiation of T follicular helper (Tfh) cells. Here we define conditions specifically enhancing Tfh differentiation and providing protection in a model of influenza infection. Tfh responses were associated with prolonged antigen presentation by dendritic cells (DCs), which maintained T cell/DC interactions into stage 3 (>72 hr) of activation. Blocking stage 3 interactions ablated Tfh generation, demonstrating a causal link between T cell-DC behaviour and functional outcomes. The current data therefore explain how duration of antigen presentation affects the dynamics of T cell-DC interactions and consequently determine Tfh cell differentiation in the developing immune response.

Abstract

The production of high affinity, class switched antibodies produced by B cells hinges on the effective differentiation of T follicular helper (Tfh) cells. Here we define conditions specifically enhancing Tfh differentiation and providing protection in a model of influenza infection. Tfh responses were associated with prolonged antigen presentation by dendritic cells (DCs), which maintained T cell/DC interactions into stage 3 (>72 hr) of activation. Blocking stage 3 interactions ablated Tfh generation, demonstrating a causal link between T cell-DC behaviour and functional outcomes. The current data therefore explain how duration of antigen presentation affects the dynamics of T cell-DC interactions and consequently determine Tfh cell differentiation in the developing immune response.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Medical Virology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:10 August 2015
Deposited On:15 Feb 2016 15:18
Last Modified:29 Aug 2017 13:58
Publisher:eLife Sciences Publications Ltd.
ISSN:2050-084X
Funders:Wellcome TrustWT085589MA to Garside P and Brewer J M, Wellcome Trust100034/Z/12/Z to MacLeod M KL
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.7554/eLife.06994
Official URL:http://elifesciences.org/content/4/e06994/article-info
PubMed ID:26258879
Other Identification Number:PMCID: PMC4558563

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