STEROIDS INHIBIT UPTAKE AND OR PROCESSING BUT NOT PRESENTATION OF ANTIGEN BY AIRWAY DENDRITIC CELLS/

Recent studies from our laboratory indicate that local and (particular ly) systemic steroids can modulate the traffic of dendritic cells (DC) through resting and inflamed airway epithelial tissues. The present r eport focuses upon the T-cell activating properties of DC, which are c ontrolled by granulocyte-macrophage colony-stimulating factor (GM-CSF) signals, and in particular the question of whether the DC-stimulating effects of GM-CSF are susceptible to regulation by steroids. We prese nt evidence that while dexamethasone inhibited GM-CSF-dependent uptake and/or processing of exogenous antigen by DC, it was ineffective in b locking the presentation of preprocessed self antigen to alloreactive T cells in a one-way mixed lymphocyte reaction (MLR). Associated GM-CS F-induced up-regulation of major histocompatability complex (MHC) clas s II and CTLA4 ligand expression by DC were also unaffected by dexamet hasone phosphate (DX), reinforcing the view that the inhibitory effect s of steroids on the T cell activating functions of DC are restricted to steps upstream from presentation of processed antigen to the T-cell receptor (TCR). These findings have potentially important implication s in relation to the use of topical steroids in the treatment of atopi c asthma, a disease in which local T-cell activation in airway tissue is a key pathogenic factor, and which furthermore is characterized by intense production of GM-CSF within the airway epithelium.