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 most effective antigen presenting cells able to activate naive T cells. Previous studies have shown that dexamethasone impaired the function of murine DC. Here, we analyzed how methylprednisolone (MP) might affect the function and maturation of human DC.


METHODS
Human DC were generated from peripheral blood mononuclear cells cultured 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 antigen uptake and down-regulated their basal expression of CD86. The expression of CD80 and CD54 by DC was slightly decreased and HLA-DR expression was not modified. MP prevented LPS-induced DC maturation as assessed by the inhibition 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 were deficient in their ability to elicit proliferative responses of CD4+CD45RA+ allogeneic T cells as well as their synthesis of interferon (IFN)-gamma, IL-5, and IL-13. CONCLUSION. Glucocorticoids exert potent suppressive effects on human DC and thereby inhibit the induction of primary T cell responses.
Vanderheyde
N
N
Laboratory of Experimental Immunology and Centre de Recherche Interuniversitaire en Vaccinologie, Université Libre de Bruxelles, Brussels, Belgium.
Verhasselt
V
V
Goldman
M
M
Willems
F
F
D000941:Antigens / Q000378:metabolism; D015703:Antigens, CD / Q000096:biosynthesis; D000954:Antigens, Surface / Q000096:biosynthesis; D018122:B7-1 Antigen / Q000096:biosynthesis; D051940:B7-2 Antigen; D002470:Cell Survival / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D004705:Endocytosis / Q000276:immunology; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000378:metabolism; D007518:Isoantibodies / Q000276:immunology; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D008775:Methylprednisolone / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000941:Antigens; D015703:Antigens, CD; D000954:Antigens, Surface; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D006684:HLA-DR Antigens; D007518:Isoantibodies; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D018664:Interleukin-12; D008775:Methylprednisolone