MHC class I-dependent Vγ4⁺ pulmonary T cells regulate αβ T cell-independent airway responsiveness

Mice exposed to aerosolized ovalbumin (OVA) develop increased airway responsiveness when deficient in γδ T cells. This finding suggests that γδ T cells function as negative regulators. The regulatory influence of γδ T cells is evident after OVA-sensitization and -challenge, and after OVA-challenge alone, but not in untreated mice. With aerosolized Abs to target pulmonary T cells, we now demonstrate that negative regulation of airway responsiveness is mediated by a small subpopulation of pulmonary γδ T cells. These cells express Vγ4 and depend in their function on the presence of IFN-γ and MHC class I. Moreover, their effect can be demonstrated in the absence of αβ T cells. This novel type of negative regulation seems to precede the development of the adaptive, antigen-specific allergic response.