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


ABSTRACT: 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.

SUBMITTER: Sutherland RM 

PROVIDER: S-EPMC5394288 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Cognate antigen engagement on parenchymal cells stimulates CD8<sup>+</sup> T cell proliferation in situ.

Sutherland Robyn M RM   Londrigan Sarah L SL   Brady Jamie L JL   Carrington Emma M EM   Marchingo Julia M JM   Heinzel Susanne S   Hodgkin Philip D PD   Graham Kate L KL   Kay Thomas W TW   Zhan Yifan Y   Lew Andrew M AM  

Nature communications 20170412


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 enc  ...[more]

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