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

Shigeki Matsubara, Katsuyuki Takeda, Niyun Jin, Masakazu Okamoto, Hiroyuki Matsuda, Yoshiki Shiraishi, Jung Won Park, Glen McConville, Anthony Joetham, Rebecca L. O'Brien, Azzeddine Dakhama, Willi K. Born, Erwin W. Gelfand

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18 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)454-463
Number of pages10
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume40
Issue number4
DOIs
Publication statusPublished - 2009 Apr 1

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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    Matsubara, S., Takeda, K., Jin, N., Okamoto, M., Matsuda, H., Shiraishi, Y., Park, J. W., McConville, G., Joetham, A., O'Brien, R. L., Dakhama, A., Born, W. K., & Gelfand, E. W. (2009). Vγ1+ T cells and tumor necrosis factor-alpha in ozone-induced airway hyperresponsiveness. American Journal of Respiratory Cell and Molecular Biology, 40(4), 454-463. https://doi.org/10.1165/rcmb.2008-0346OC