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

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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 hours) 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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Robert A Benson

Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom

Competing interests
The authors declare that no competing interests exist.
Megan KL MacLeod

Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom

Competing interests
The authors declare that no competing interests exist.
Benjamin G Hale

Institute of Medical Virology, University of Zurich, Zurich, Switzerland

Competing interests
The authors declare that no competing interests exist.
Agapitos Patakas

Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom

Competing interests
The authors declare that no competing interests exist.
Paul Garside

Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom

Competing interests
The authors declare that no competing interests exist.
James M Brewer

Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom

For correspondence
Robert.Benson@glasgow.ac.uk

Competing interests
The authors declare that no competing interests exist.

Ethics

Animal experimentation: All animals were specified pathogen free and maintained under standard animal house conditions at the University of Glasgow in accordance with local and UK Home Office Regulations.

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This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.