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

RA Benson, MKL MacLeod, BG Hale, A Patakas… - Elife, 2015 - elifesciences.org
RA Benson, MKL MacLeod, BG Hale, A Patakas, P Garside, JM Brewer
Elife, 2015elifesciences.org
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 …
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.
DOI: http://dx.doi.org/10.7554/eLife.06994.001
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