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

Area of Science:

• Immunology
• Cell Biology
• Microbiology

Background:

• Interleukin-17A (IL-17A) is a pro-inflammatory cytokine vital in immune responses at mucosal sites.
• Gamma delta T cells (γδ T cells) are known IL-17A producers, but specific subsets and their functions require further definition.

Purpose of the Study:

• To identify and characterize a distinct subset of γδ T cells responsible for rapid IL-17A production.
• To elucidate the mechanisms and in vivo relevance of this IL-17A-producing γδ T-cell subset.

Main Methods:

• Flow cytometry gating strategy based on CD3 expression levels to identify γδ T-cell subsets.
• Analysis of T-cell receptor (TCR) Vγ6/Vδ1 expression.
• Assessment of cytokine production (IL-17A, IFN-γ) and response to stimuli (IL-23, NLRP3 inflammasome).
• Evaluation in models of pneumococcal infection and skin inflammation.

Main Results:

• A CD3(bright) γδ T-cell subset with an effector memory phenotype was identified as a rapid producer of IL-17A, but not interferon-γ.
• These cells uniformly express the Vγ6/Vδ1(+) TCR and are enriched in lungs and skin.
• Their function is dependent on retinoic acid receptor-related orphan receptor gammat (RORγt) and influenced by endogenous flora.
• The response involves IL-23 and NLRP3 inflammasome-dependent IL-1β, with prompt activation during pneumococcal infection and skin inflammation.

Conclusions:

• A novel gating strategy based on CD3 signal intensity allows specific analysis of IL-17-producing Vγ6/Vδ1(+) γδ T cells.
• This γδ T-cell subset plays a critical role in host defense against respiratory and skin inflammatory conditions.