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CD3 signals on gammadelta T cells identify IL-17A-producing Vgamma6Vdelta1 T cells


Paget, C; Chow, MT; Gherardin, NA; Beavis, PA; Uldrich, AP; Duret, H; Hassane, M; Souza-Fonseca-Guimaraes, F; Mogilenko, DA; Staumont-Salle, D; Escalante, NK; Hill, GR; Neeson, P; Ritchie, DS; Dombrowicz, D; Mallevaey, T; Trottein, F; Belz, GT; Godfrey, DI; Smyth, MJ
2014-11-11
Immunol Cell Biol
Journal Article in press
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. gammadelta T cells are recognized as IL-17 producers, but based on the level of CD3 expression, we now define the remarkable ability of a CD3bright gammadelta T-cell subset with an effector memory phenotype to rapidly produce IL-17A, but not interferon-gamma. CD3bright gammadelta T cells uniformly express the canonical germline encoded Vgamma6/Vdelta1+ 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-1beta. Finally, we demonstrated that IL-17-producing CD3bright gammadelta 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 Vgamma6/Vdelta1+ T cells based on the level of CD3 signals. Using this gating strategy, our data reinforce the crucial role of this gammadelta T-cell subset in respiratory and skin disorders.Immunology and Cell Biology advance online publication, 11 November 2014; doi:10.1038/icb.2014.94.
NPG
Molecular Immunology
10.1038/icb.2014.94
© 2014 Australasian Society for Immunology

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