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Cognate antigen engagement on parenchymal cells stimulates CD8+ T cell proliferation in situ.

Robyn M SutherlandSarah L LondriganJamie L BradyEmma M CarringtonJulia M MarchingoSusanne HeinzelPhilip D HodgkinKate L GrahamThomas W KayYifan ZhanAndrew M Lew
Published in: Nature communications (2017)
T-cell responses are initiated upon cognate presentation by professional antigen presenting cells in lymphoid tissue. T cells then migrate to inflamed tissues, but further T-cell stimulation in these parenchymal target sites is not well understood. Here we show that T-cell expansion within inflamed tissues is a distinct phase that is neither a classical primary nor classical secondary response. This response, which we term 'the mezzanine response', commences within days after initial antigen encounter, unlike the secondary response that usually occurs weeks after priming. A further distinction of this response is that T-cell proliferation is driven by parenchymal cell antigen presentation, without requiring professional antigen presenting cells, but with increased dependence on IL-2. The mezzanine response might, therefore, be a new target for inhibiting T-cell responses in allograft rejection and autoimmunity or for enhancing T-cell responses in the context of microbial or tumour immunity.
Keyphrases
  • cell proliferation
  • induced apoptosis
  • cell cycle arrest
  • gene expression
  • case report
  • oxidative stress
  • microbial community
  • cell death
  • preterm infants
  • bone marrow
  • cell therapy
  • heat shock
  • heat shock protein