Pulmonary dendritic cells and alveolar macrophages are regulated by gamma delta T cells during the resolution of S. pneumoniae-induced inflammation

γδ T cells commonly associate with mucosal and epithelial sites, fulfilling a variety of immunoregulatory functions. While lung γδ T cells have well-characterized pro-inflammatory activity, their potential role in the resolution of lung inflammation has yet to be explored in any detail. Indeed, given the importance of minimizing inflammation, the cellular mechanisms driving the resolution of lung inflammation are poorly understood. Using a murine model of acute Streptococcus pneumoniae-mediated lung inflammation, we now show that resolution of inflammation following bacterial clearance is associated with a > 30-fold increase in γδ T-cell number. Although inflammation eventually resolves in TCRδ−/− mice, elevated numbers of alveolar macrophages and pulmonary dendritic cells, and the appearance of well-formed granulomas in lungs of TCRδ−/− mice, together indicated a role for γδ T cells in regulating mononuclear phagocyte number. Ex vivo, both alveolar macrophages and pulmonary dendritic cells were susceptible to lung γδ T cell-mediated cytotoxicity, the first demonstration of such activity against a dendritic cell population. These findings support a model whereby expansion of γδ T cells helps restore mononuclear phagocyte numbers to homeostatic levels, protecting the lung from the consequences of inappropriate inflammation.