Inhibition of human dendritic cell functions by methylprednisolone

Transplantation. 1999 May 27;67(10):1342-7. doi: 10.1097/00007890-199905270-00009.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens / metabolism
  • Antigens, CD / biosynthesis
  • Antigens, Surface / biosynthesis
  • B7-1 Antigen / biosynthesis
  • B7-2 Antigen
  • Cell Survival / drug effects
  • Dendritic Cells / cytology
  • Dendritic Cells / drug effects*
  • Dendritic Cells / physiology*
  • Endocytosis / immunology
  • HLA-DR Antigens / biosynthesis
  • Humans
  • Intercellular Adhesion Molecule-1 / biosynthesis
  • Interleukin-12 / metabolism
  • Isoantibodies / immunology
  • Membrane Glycoproteins / biosynthesis
  • Methylprednisolone / pharmacology*
  • T-Lymphocytes / immunology
  • Tumor Necrosis Factor-alpha / metabolism


  • Antigens
  • Antigens, CD
  • Antigens, Surface
  • B7-1 Antigen
  • B7-2 Antigen
  • CD86 protein, human
  • HLA-DR Antigens
  • Isoantibodies
  • Membrane Glycoproteins
  • Tumor Necrosis Factor-alpha
  • Intercellular Adhesion Molecule-1
  • Interleukin-12
  • Methylprednisolone