Pulmonary dendritic cells and alveolar macrophages are regulated by gammadelta T cells during the resolution of S. pneumoniae-induced inflammation.
gammadelta T cells commonly associate with mucosal and epithelial sites, fulfilling a variety of immunoregulatory functions. While lung gammadelta 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 gammadelta T-cell number. Although inflammation eventually resolves in TCR delta(-/-) mice, elevated numbers of alveolar macrophages and pulmonary dendritic cells, and the appearance of well-formed granulomas in lungs of TCR delta(-/-) mice, together indicated a role for gammadelta T cells in regulating mononuclear phagocyte number. Ex vivo, both alveolar macrophages and pulmonary dendritic cells were susceptible to lung gammadelta T cell-mediated cytotoxicity, the first demonstration of such activity against a dendritic cell population. These findings support a model whereby expansion of gammadelta T cells helps restore mononuclear phagocyte numbers to homeostatic levels, protecting the lung from the consequences of inappropriate inflammation.
Kirby
A C
AC
Immunology and Infection Unit, Department of Biology, University of York and Hull York Medical School, UK. ak510@york.ac.uk
Newton
D J
DJ
Carding
S R
SR
Kaye
P M
PM
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D005434:Flow Cytometry; D008168:Lung / Q000276:immunology*; D016676:Macrophages, Alveolar / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011018:Pneumonia, Pneumococcal / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D013194:Staining and Labeling; D013296:Streptococcus pneumoniae; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D016692:Receptors, Antigen, T-Cell, gamma-delta