GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR OVERRIDES THE IMMUNOSUPPRESSIVE FUNCTION OF CORTICOSTEROIDS ON RAT PULMONARY DENDRITIC CELLS

Pulmonary dendritic cells (DC) are present in extremely small numbers, but they are the most potent antigen-presenting cells in the lungs, P ure populations of DC can be isolated from the lung following collagen digestion, Percoll gradient centrifugation, removal of phagocytic cel ls and flow cytometric sorting for cells which exhibit high levels of surface major histocompatibility complex (MHC) class II molecules. Exo genous GM-CSF enhances this immunostimulatory capacity of the pulmonar y DC, Soluble factors produced by type II airway epithelial cells and interstitial macrophages also enhance the immunostimulating capacity o f pulmonary DC while alveolar macrophages suppress it. Thus, the funct ion of DC may be regulated by locally produced cytokines, Corticostero ids are widely used as immunosuppressive agents in pharmacotherapy. Wh ile these agents are known to inhibit T cell proliferation and macroph age activation, their effects on DC are not known. We found that dexam ethasone (Dex) pretreatment resulted in about a 50% reduction in the i mmunostimulatory capacity of rat pulmonary DC, This was associated wit h downregulation of MHC class II (Ia) expression. Dex-induced suppress ion of DC function could be restored with GM-CSF. We conclude that cor ticosteroids downregulate antigen-presenting capacity by direct suppre ssion of pulmonary DC. This immunosuppressive effect of corticosteroid s on DC may, however, be abrogated by exogenous GM-CSF. Corticosteroid s and GM-CSF are therapeutic agents with potent direct immunomodulatin g effects on DC.