Vγ1+ T cells and tumor necrosis factor-alpha in ozone-induced airway hyperresponsiveness

γδ T cells regulate airway reactivity, but their role in ozone (O ₃)- induced airway hyperresponsiveness (AHR) is not known. Our objective was to determine the role of γδ T cells in O ₃-induced AHR. Different strains of mice, including those that were genetically manipulated or antibody-depleted to render them deficient in total γδTcellsorspecific subsets of γδTcells, were exposedto2.0 ppm of O ₃ for 3 hours. Airway reactivity to inhaled methacholine, airway inflammation, and epithelial cell damage were monitored.Exposure of C57BL/6 mice to O ₃ resulted in a transient increase in airway reactivity, neutrophilia, and increased numbers of epithelial cells in the lavage fluid. TCR-δ ^-/- mice did not develop AHR, although they exhibited an increase in neutrophils and epithelial cells in the lavage fluid. Similarly, depletion of γδ T cells in wild-type mice suppressed O ₃-induced AHR without influencing airway inflammation or epithelial damage. Depletion of VΓ1+, but notofVγ4+Tcells, reduced O ₃-induced AHR, and transfer of total γδ T cells or Vγ1+ T cells to TCR-δ ^-/- mice restoredAHR. After transferofVγ1+ cells to TCR-δ ^-/- mice, restoration of AHR after O ₃ exposure was blocked by anti- TNF-α.However, AHR couldberestoredinTCR-δ ^-/- mice by transfer of γδ T cells from TNF-α-deficient mice, indicating that another cell type was the sourceof TNF-α. These results demonstrate that TNF-α andactivationofVγ1+ γδTcellsarerequiredforthedevelopmentof AHR after O ₃ exposure.