Human lung γδ T cells maintain functionality during inflammatory lung disease

Area of Science:

• Immunology
• Respiratory Medicine

Background:

• Gamma delta (γδ) T cells are crucial for mucosal immunity and tissue repair.
• The human lung environment's impact on γδ T cell function, especially during inflammation, is not well understood.

Purpose of the Study:

• To investigate how the lung environment and interstitial lung disease (ILD) affect γδ T cell functionality.
• To compare γδ T cells from lung tissue with those from matched hilar lymph nodes (LN).

Main Methods:

• Analysis of lung and hilar LN tissues from deceased donors and ILD patients.
• High-parameter spectral flow cytometry to assess phenotype and ex vivo function.
• Stimulation assays to measure effector functions like cytokine production and epithelial cell proliferation.

Main Results:

• Lung γδ T cells show enrichment of an effector memory phenotype compared to regional LN.
• γδ T cells from deceased donors' lungs and LN exhibit similar functions.
• While ILD lung γδ T cells largely retain cytokine production, it's diminished compared to LN.
• Lung γδ T cells consistently maintain polyfunctional expression of granzyme B (GzmB), interferon-γ (IFNγ), and tumor necrosis factor (TNFα) across all groups.

Conclusions:

• Human lung γδ T cells are phenotypically distinct from those in LN.
• Lung γδ T cells exhibit conserved effector functions, including antimicrobial and tissue repair capacities, even within a fibrotic lung environment.