Differential effects of corticosteroids during different stages of dendritic cell maturation

Dendritic cell (DC) maturation is a complex process involving many cell fun ctions. We have studied how the exposure of DC to corticosteroids at differ ent stages of DC maturation affects priming and the expansion of different subsets of CD4(+) T cells. Growth factor-dependent DC lines and fresh bone marrow-derived DC were used. When exposed to inflammatory stimuli, immature DC previously treated with dexamethasone were unable to undergo full matur ation and were unable to prime Th1 cells efficiently. There was specific an d significant reduction in the number of IFN-gamma-producing effector cell (shown by intracellular cytokine staining) and also in the amount of IFN-ga mma produced. Interestingly, the number of IL-4-producing T cells and the a mount of IL-4 synthesis was not significantly altered. Furthermore, multipl e restimulation of T cells with these DC gave rise to a subpopulation of T regulatory cells (Tr1) which were negative for IFN-gamma and IL-4 but were IL-10 positive. In contrast, when DC were activated with lipopolysaccharide prior to dexamethasone treatment, the suppressive effect of glucocorticoid s was not significant. Thus, the stage of DC maturation influences the inhi bitory effect of corticosteroids. By arresting DC maturation, corticosteroi ds strongly reduce cell-mediated Th1 responses and allow the selective expa nsion of Tr1 cells.