Pulmonary dendritic cells from chronic obstructive pulmonary disease patients suppress lung immune responses through induction of regulatory T cells

Defective Th immunity is considered to be implicated in the enhanced vulnerability of Chronic Obstructive Pulmonary Disease (COPD) patients to lower respiratory infections and lung cancer. Tolerogenic dendritic cells (DCs) and regulatory T cells (Tregs) are critical in the suppression of Th immunity. Their role in COPD is elusive. We hypothesized that pulmonary DCs in COPD exhibit tolerogenic properties and suppress lung Th responses through induction of Tregs. CD1c+ DCs and CD3+ T cells were isolated from the lungs of COPD patients (n=17), smokers (n=16) and never-smokers (n=4). DC maturation prior and upon LPS exposure were examined. The effects of pulmonary DCs on lung Th cell responses and on the induction of Tregs were investigated. Pulmonary DCs from COPD patients and smokers express decreased levels of co-stimulatory molecules (CD40/86) compared to never-smokers at baseline (p<0.01). Upon LPS exposure, only DCs from COPD patients fail to upregulate costimulatory molecules. Pulmonary DCs from COPD patients induce decreased proliferation of autologous lung CD4+ and CD8+ T cells compared to DCs from smokers (p<0.001). CD4+ T cells treated with DCs from COPD patients, but not from smokers, express increased levels of the immunosuppressive cytokine IL-10 (p<0.01) and suppress Th responses in in vitro suppression assays. Our results reveal that lung DCs from COPD patients suppress lung immune responses through induction of Tregs. This novel immunoregulatory circuit has important clinical implications for the enhanced vulnerability of COPD patients to respiratory infections and lung cancer. *These authors contributed equally. Funded by Thorax.