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Priming of qualitatively superior human effector CD8+ T cells using TLR8 ligand combined with FLT3 ligand

Lissina, Anna, Briceño, Olivia, Afonso, Georgia, Larsen, Martin, Gostick, Emma, Price, David, Mallone, Roberto and Appay, Victor 2016. Priming of qualitatively superior human effector CD8+ T cells using TLR8 ligand combined with FLT3 ligand. The Journal of Immunology 196 (1) , pp. 256-263. 10.4049/jimmunol.1501140
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The quality of Ag-specific CD8+ T cell responses is central to immune efficacy in infectious and malignant settings. Inducing effector CD8+ T cells with potent functional properties is therefore a priority in the field of immunotherapy. However, the optimal assessment of new treatment strategies in humans is limited by currently available testing platforms. In this study, we introduce an original model of in vitro CD8+ T cell priming, based on an accelerated dendritic cell coculture system, which uses unfractionated human PBMCs as the starting material. This approach enables the rapid evaluation of adjuvant effects on the functional properties of human CD8+ T cells primed from Ag-specific naive precursors. We demonstrate that a selective TLR8 agonist, in combination with FLT3L, primes high-quality CD8+ T cell responses. TLR8L/FLT3L-primed CD8+ T cells displayed enhanced cytotoxic activity, polyfunctionality, and Ag sensitivity. The acquisition of this superior functional profile was associated with increased T-bet expression induced via an IL-12–dependent mechanism. Collectively, these data validate an expedited route to vaccine delivery or optimal T cell expansion for adoptive cell transfer.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
Publisher: American Association of Immunologists
ISSN: 0022-1767
Date of First Compliant Deposit: 22 June 2017
Date of Acceptance: 8 October 2015
Last Modified: 18 Oct 2019 18:31

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