Dexamethasone and Cyclosporin A Affect the Maturation of Monocyte-Derived Dendritic Cells Differently

Abstract

In contrast to the confirmed effects of glucocorticoids (GCs) and cyclosporin A (CyA) on T cells, the effects of both agents on antigen-presenting cells (APCs), especially on dendritic cells (DCs), are still poorly understood. In this study, we cultured monocyte-derived DCs (MoDCs) under a variety of stimulations in the presence or absence of these immunosuppressants and compared their effects on the activation of MoDCs by these stimulations. The stimulations used were the following: three bacterial toxins, including lipopolysaccharide (LPS), staphylococcal enterotoxin A (SEA) and streptococcal pyrogenic exotoxin A (SPEA), the combination of IL-1β and TNF-α, and an agonistic anti-CD40 antibody. All of these stimulations increased the expression of CD54, CD83, CD86, and HLA-DR antigen, and the production of TNF-α in MoDCs. When MoDCs were treated with dexamethasone (Dex) during the stimulation, Dex significantly suppressed the augmentation of CD86 expression and TNF-α production induced by all of these stimulations. In contrast, when MoDCs were treated with CyA, it inhibited only the effects induced by the superantigens, SEA and SPEA, but not that induced by LPS, the combination of cytokines, or anti-CD40 antibody. The augmentation of CD54 or HLA-DR antigen expression was not significantly suppressed by either Dex or by CyA. When we used MoDCs pretreated with each of these stimulations + Dex or + CyA as APCs, however, significant suppression of T cell proliferation was observed only in the case of the pretreatment with IL-1β/TNF-α + Dex. The allogeneic T cell stimulation by MoDCs pretreated with the other combinations did not significantly differ from that treated with the stimulation alone. Our present study succeeded in demonstrating a clear difference between Dex and CyA in the activation of MoDCs. These differences may induce a significant difference in their final immunological responses.