CD3bright signals on γδ T cells identify IL‐17A‐producing Vγ6Vδ1+ T cells

C Paget, M T Chow, N A Gherardin, P A Beavis, A P Uldrich, H Duret, M Hassane, F Souza‐Fonseca‐Guimaraes, D A Mogilenko, D Staumont‐Sallé, N K Escalante, G R Hill, P Neeson, D S Ritchie, D Dombrowicz, T Mallevaey, F Trottein, G T Belz, D I Godfrey, M J Smyth

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. CD3(bright) 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.Immunology and Cell Biology advance online publication, 11 November 2014; doi:10.1038/icb.2014.94.