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

Immunol Cell Biol. 2015 Feb;93(2):198-212. doi: 10.1038/icb.2014.94. Epub 2014 Nov 11.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Aminoquinolines / pharmacology
  • Animals
  • CD3 Complex / chemistry
  • CD3 Complex / metabolism*
  • Carrier Proteins / metabolism
  • Germ Cells / drug effects
  • Homeostasis / drug effects
  • Imiquimod
  • Immunity
  • Inflammasomes / drug effects
  • Inflammasomes / metabolism
  • Interleukin-17 / biosynthesis*
  • Interleukin-1beta / metabolism
  • Interleukin-23
  • Lung / drug effects
  • Lung / immunology
  • Lymphocyte Subsets / drug effects
  • Lymphocyte Subsets / immunology
  • Male
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / metabolism
  • Phenotype
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism*
  • Skin / drug effects
  • Skin / immunology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*


  • Aminoquinolines
  • CD3 Complex
  • Carrier Proteins
  • Inflammasomes
  • Interleukin-17
  • Interleukin-1beta
  • Interleukin-23
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Receptors, Antigen, T-Cell, gamma-delta
  • T-cell receptor Vgamma6, mouse
  • Imiquimod