Inhibition of human dendritic cell functions by methylprednisolone

Background, The aim of this study was to better define how glucocorticoids influence primary human T cell responses. Dendritic cells (DC*) are the mos t effective antigen presenting cells able to activate naive T cells. Previo us studies have shown that dexamethasone impaired the function of murine DC , Here, we analyzed how methylprednisolone (RIP) might affect the function and maturation of human DC, Methods. Human DC were generated from peripheral blood mononuclear cells cu ltured in granulocyte macrophage-colony stimulating factor and interleukin (IL)-4. DC maturation was induced either by lipopolysaccharide (LPS) or by fibroblast transfected with the CD40-ligand gene (3T6-CD40L), DC phenotype was characterized by flow cytometric analysis, their cytokine production by ELISA. The ability of DC to activate naive T cells was evaluated in mixed leukocyte reactivity. Results. Although MP did not affect viability of DC, it enhanced their anti gen uptake and down-regulated their basal expression of CD86. The expressio n of CD80 and CD54 by DC was slightly decreased and HLA-DR expression was n ot modified. MP prevented LPS-induced DC maturation as assessed by the inhi bition of CD86, CD80 and CD54 up-regulation, CD83 induction and production of TNF-alpha, IL-6, and IL-12. in contrast, when DC were stimulated by 3T6- CD40L, MP prevented only the synthesis of IL-12. Moreover, MP-treated DC we re deficient in their ability to elicit proliferative responses of CD4(+)CD 45RA(+) allogeneic T cells as well as their synthesis of interferon (IFN)-g amma, IL-5, and IL-13. Conclusion. Glucocorticoids exert potent suppressive effects on human DC an d thereby inhibit the induction of primary T cell responses.