Impact of psoralen/UVA-treatment on survival, activation, and immunostimulatory capacity of monocyte-derived dendritic cells

Transplantation. 2008 Mar 15;85(5):757-66. doi: 10.1097/TP.0b013e31816650f6.


Background: Extracorporeal Photopheresis (ECP) has been shown to be an effective treatment of graft-versus-host disease, solid organ graft rejection, and other T-cell-mediated diseases. The mechanisms of action of ECP include lymphocyte apoptosis, cytokine modulation, and the induction of regulatory T cells. It has been suggested that dendritic cells (DCs) are more resistant to ECP-induced apoptosis and might be directly modulated by ECP. We tested this hypothesis using in vitro Psoralen/UVA (PUVA) treatment as an in vitro model of ECP.

Methods: Monocyte-derived DCs (mo-DCs) were treated with 8-methoxypsoralen /UVA and analyzed for surface molecule expression, apoptosis markers, endocytosis, and migratory and immunostimulatory capacity. Mo-DC phenotype and cytokine secretion was tested after CD40L stimulation. Naive T cells stimulated with PUVA-treated mo-DCs were tested for Th1/Th2 cytokine secretion and associated chemokine receptor patterns.

Results: DCs underwent apoptosis after in vitro PUVA and in vivo ECP. In vitro, the induction of apoptosis was preceded by partial maturation of immature mo-DCs. PUVA-treated immature mo-DCs also exhibited enhanced migratory and immunostimulatory capacity. However, mo-DCs stimulation through CD40 ligation was abrogated and interleukin (IL)-12 secretion was abolished 24 hr after PUVA treatment. PUVA-treated mo-DCs skewed naive T cells toward a Th2 response as defined by increased IL-4, IL-10, and IL-13 and decreased interferon-gamma levels, and the expression of the Th2-associated chemokine receptors CCR4 and CCR10. The observed Th2 shift was partially reversed by exogenous IL-12.

Conclusion: These data suggest that direct modulation of DC function as well as apoptosis contribute to the immunoregulatory effects of ECP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD40 Ligand / drug effects
  • CD40 Ligand / physiology
  • Cell Culture Techniques / methods
  • Cell Division / drug effects
  • Cell Movement / drug effects
  • Cell Survival / drug effects
  • Cytokines / analysis
  • Dendritic Cells / cytology*
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Dendritic Cells / radiation effects
  • Endocytosis / drug effects
  • Flow Cytometry
  • Furocoumarins / pharmacology*
  • Humans
  • Lymphocyte Activation / drug effects
  • Monocytes / cytology
  • Monocytes / immunology*
  • Ultraviolet Rays


  • Cytokines
  • Furocoumarins
  • CD40 Ligand