CD3bright signals on [gamma][delta] T cells identify IL-17A-producing V[gamma]6V[delta]1+ T cells

• Published in: Immunology and cell biology 2015-02, Vol.93 (2), p.198
• Main Authors: Paget, C, Chow, M T, Gherardin, N A, Beavis, P A, Uldrich, A P, Duret, H, Hassane, M, Souza-fonseca-guimaraes, F, Mogilenko, D A, Staumont-sallé, D, Escalante, N K, Hill, G R, Neeson, P, Ritchie, D S, Dombrowicz, D, Mallevaey, T, Trottein, F, Belz, G T, Godfrey, D I, Smyth, M J
• Format: Article
• Language: English
• ISSN: 0818-9641; 1440-1711
• DOI: 10.1038/icb.2014.94

Interleukin-17A (IL-17A) is a pro-inflammatory cytokine that has an important role at mucosal sites in a wide range of immune responses including infection, allergy and auto-immunity. γδ T cells are recognized as IL-17 producers, but based on the level of CD3 expression, we now define the remarkable ability of a CD3 bright γδ T-cell subset with an effector memory phenotype to rapidly produce IL-17A, but not interferon-γ. CD3bright γδ T cells uniformly express the canonical germline encoded Vγ6/Vδ1+ T-cell receptor. They are widely distributed with a preferential representation in the lungs and skin are negatively impacted in the absence of retinoic acid receptor-related orphan receptor gammat expression or endogenous flora. This population responded rapidly to various stimuli in a mechanism involving IL-23 and NOD-like receptor family, pyrin domain containing 3 (NLRP3)-inflammasome-dependent IL-1β. Finally, we demonstrated that IL-17-producing CD3 bright γδ T cells responded promptly and strongly to pneumococcal infection and during skin inflammation. Here, we propose a new way to specifically analyze IL-17-producing Vγ6/Vδ1+ T cells based on the level of CD3 signals. Using this gating strategy, our data reinforce the crucial role of this γδ T-cell subset in respiratory and skin disorders.