The Vγ4+ pulmonary subset of γδ T cells regulates innate airway responsiveness in the absence of αβ 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, Vγ4+ cells preferentially increased in number following airway challenge. Depletion of Vγ4+ cells before the challenge substantially increased AHR in these mice, but had no effect on airway responsiveness in normal, nonchallenged mice. Depletion of Vγ1 + cells had no effect on AHR, and depletion of all TCR-δ + cells was no more effective than depletion of Vγ4 + cells alone. Adoptively transferred pulmonary lymphocytes containing Vγ4+ cells inhibited AHR, but lost this ability when Vγ4+ 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 Vγ4+ cells, although cytokine-producing αβ T cells in the lung increased. These findings establish Vγ4+ γδ T cells as negative regulators of AHR and show that their regulatory effect bypasses much of the allergic inflammatory response coincident with AHR.
All Science Journal Classification (ASJC) codes
- Immunology and Allergy