GLUCOCORTICOIDS DOWN-REGULATE DENDRITIC CELL-FUNCTION IN-VITRO AND IN-VIVO

Exogenous glucocorticoid hormones are widely used as therapeutical age nts, whereas endogenous glucocorticoids may act as physiological immun osuppressants involved in the control of immune and inflammatory respo nses. The optimal activation of T lymphocytes requires two distinct si gnals: the major histocompatibility complex-restricted presentation of the antigen and an additional co-stimulatory signal provided by the a ntigen-presenting cells. There is ample evidence that, among the cells able to present the antigen, the dendritic cells (DC) have the unique property to activate antigen-specific, naive T cells in vitro and in vivo, and are therefore required for the induction of primary immune r esponses. In this work, we tested whether glucocorticoids affected the capacity of DC to sensitize naive T cells. Our data show that, in vit ro, the steroid hormone analog dexamethasone (Dex) affects the viabili ty of DC, selectively downregulates the expression of co-stimulatory m olecules on viable DC, and strongly reduces their immunostimulatory pr operties. In vivo, a single injection of Dex results in impaired antig en presenting function, a finding which correlates with reduced number s of splenic DC. These results show that glucocorticoids regulate DC m aturation and immune function in vitro and in vivo and suggest that th is mechanism may play a role in preventing overstimulation of the immu ne system.