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V1+ T Cells and Tumor Necrosis Factor-Alpha in Ozone-Induced Airway Hyperresponsiveness

¹ Division of Cell Biology, Department of Pediatrics, and ² Integrated Department of Immunology, National Jewish Health and the University of Colorado Health Sciences Center, Denver, Colorado

Correspondence and requests for reprints should be addressed to Erwin W. Gelfand, M.D., National Jewish Health, 1400 Jackson Street, Denver, CO 80206. E-mail: gelfande{at}njhealth.org

T cells regulate airway reactivity, but their role in ozone (O₃)-induced airway hyperresponsiveness (AHR) is not known. Our objective was to determine the role of T cells in O₃-induced AHR. Different strains of mice, including those that were genetically manipulated or antibody-depleted to render them deficient in total T cells or specific subsets of T cells, were exposed to 2.0 ppm of O₃ for 3 hours. Airway reactivity to inhaled methacholine, airway inflammation, and epithelial cell damage were monitored. Exposure of C57BL/6 mice to O₃ resulted in a transient increase in airway reactivity, neutrophilia, and increased numbers of epithelial cells in the lavage fluid. TCR-^–/– mice did not develop AHR, although they exhibited an increase in neutrophils and epithelial cells in the lavage fluid. Similarly, depletion of T cells in wild-type mice suppressed O₃-induced AHR without influencing airway inflammation or epithelial damage. Depletion of V1+, but not of V4+ T cells, reduced O₃-induced AHR, and transfer of total T cells or V1+ T cells to TCR-^–/– mice restored AHR. After transfer of V1+ cells to TCR-^–/– mice, restoration of AHR after O₃ exposure was blocked by anti–TNF-. However, AHR could be restored in TCR-^–/–mice by transfer of T cells from TNF-–deficient mice, indicating that another cell type was the source of TNF-. These results demonstrate that TNF- and activation of V1+ T cells are required for the development of AHR after O₃ exposure.

Key Words: ozone • airway responsiveness • T cells • TNF-

CLINICAL RELEVANCE This article demonstrates for the first time the essential role of a unique subset of T lymphocytes in the development of ozone-induced airway hyperresponsiveness.

 

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