title: Antigen presentation kinetics control T cell/dendritic cell interactions and follicular helper T cell generation in vivo.
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 (&gt;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.
authors.affiliation: Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Benson
authors.affiliation: Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Megan K L
authors.initials: MK
authors.lastname: MacLeod
authors.affiliation: Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
authors.forename: Benjamin G
authors.initials: BG
authors.lastname: Hale
authors.affiliation: Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Agapitos
authors.initials: A
authors.lastname: Patakas
authors.affiliation: Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Garside
authors.affiliation: Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
authors.forename: James M
authors.identifier: http://orcid.org/0000-0001-7933-0915
authors.initials: JM
authors.lastname: Brewer
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D002450:Cell Communication; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000502:physiology*; D008213:Lymphocyte Activation; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology*
keywords: T follicular helper; antibody; antigen presentation; immunology; influenza vaccine; mouse; multiphoton; viruses