γδ T cells contribute to the systemic immunoglobulin E response and local B-cell reactivity in allergic eosinophilic airway inflammation

Abstract

Allergic airway inflammation induced in mice is T-cell dependent and recruitment of eosinophils to airspaces requires both αβ and γδ T cells. From previous studies it is evident that αβ T cells are essential for the allergic T helper type 2 (Th2)-like response, while the mechanistic contribution of γδ T cells is still unclear. In this study, we have investigated the role of γδ T cells in allergic airway eosinophilia induced by ovalbumin hypersensitivity. By comparing the responsiveness to sensitizing allergen of wild-type mice with that of T-cell receptor γδ knockout mice (TCRγδ KO) we demonstrated that mice lacking γδ T cells are defective in the systemic ovalbumin-specific immunoglobulin E (IgE) response. Furthermore, after aerosol challenge with allergen, γδ T-cell deficient mice exhibited a significantly decreased migration of B cells and natural killer cells to airways and reduced levels of allergen-specific IgG and IgA in bronchoalveolar lavage fluid. The role for B cells in the airway inflammation was indicated by the impaired ability of mice lacking functional B cells to evoke an eosinophilic response. The diminished eosinophilia in TCRγδ KO mice could not be explained by a defective Th2 activation since these mice displayed a normal IgG response in serum and an unaffected IG2b/IgG1 ratio in airways. Analysis of immunoregulatory cytokines in isolated lung tissue, thoracic lymph nodes and spleen further supported the notion that these mice are able to evoke a sufficient activation of T helper cells and that γδ T cells are not required for maintaining the Th2 profile. These results indicate that γδ T cells contribute to allergic airway inflammation by pathways separate from classical Th2 immune activation.