V gamma 4+ gamma delta T cells regulate airway hyperreactivity to methacholine in ovalbumin-sensitized and challenged mice

• Published in: The Journal of immunology (1950) 2003-09, Vol.171 (6), p.3170-3178
• Main Authors: Hahn, Youn-Soo, Taube, Christian, Jin, Niyun, Takeda, Katsuyuki, Park, Jung-Won, Wands, J M, Aydintug, M Kemal, Roark, Christina L, Lahn, Michael, O'Brien, Rebecca L, Gelfand, Erwin W, Born, Willi K
• Format: Article
• Language: English
• Subjects: Adoptive Transfer; Animals; Bronchial Hyperreactivity - immunology; Bronchial Hyperreactivity - pathology; Bronchial Hyperreactivity - prevention & control; Cytokines - biosynthesis; Female; Goblet Cells - pathology; Hyperplasia; Immunization; Injections, Intraperitoneal; Lymphocyte Count; Lymphocyte Depletion; Methacholine Chloride - administration & dosage; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Ovalbumin - administration & dosage; Ovalbumin - immunology; Pulmonary Alveoli - cytology; Pulmonary Alveoli - immunology; Pulmonary Alveoli - metabolism; Pulmonary Eosinophilia - immunology; Pulmonary Eosinophilia - pathology; Receptors, Antigen, T-Cell, alpha-beta - biosynthesis; Receptors, Antigen, T-Cell, gamma-delta - biosynthesis; Receptors, Antigen, T-Cell, gamma-delta - physiology; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; T-Lymphocyte Subsets - transplantation; Up-Regulation - immunology
• ISSN: 0022-1767
• DOI: 10.4049/jimmunol.171.6.3170

The Vgamma4(+) pulmonary subset of gammadelta T cells regulates innate airway responsiveness in the absence of alphabeta T cells. We now have examined the same subset in a model of allergic airway disease, OVA-sensitized and challenged mice that exhibit Th2 responses, pulmonary inflammation, and airway hyperreactivity (AHR). In sensitized mice, Vgamma4(+) cells preferentially increased in number following airway challenge. Depletion of Vgamma4(+) cells before the challenge substantially increased AHR in these mice, but had no effect on airway responsiveness in normal, nonchallenged mice. Depletion of Vgamma1(+) cells had no effect on AHR, and depletion of all TCR-delta(+) cells was no more effective than depletion of Vgamma4(+) cells alone. Adoptively transferred pulmonary lymphocytes containing Vgamma4(+) cells inhibited AHR, but lost this ability when Vgamma4(+) cells were depleted, indicating that these cells actively suppress AHR. Eosinophilic infiltration of the lung and airways, or goblet cell hyperplasia, was not affected by depletion of Vgamma4(+) cells, although cytokine-producing alphabeta T cells in the lung increased. These findings establish Vgamma4(+) gammadelta T cells as negative regulators of AHR and show that their regulatory effect bypasses much of the allergic inflammatory response coincident with AHR.