Extracorporeal photopheresis efficiently impairs the proinflammatory capacity of human 6-sulfo LacNAc dendritic cells.

Abstract

BACKGROUND:

Extracorporeal photopheresis (ECP) emerged as a promising treatment modality for steroid-refractory graft-versus-host disease (GVHD), which represents a major complication of allogeneic hematopoietic stem-cell transplantation. Dendritic cells (DCs) display an extraordinary capacity to induce T-cell responses and play a crucial role in the initiation and maintainance of GVHD. This study evaluated the direct impact of ECP on the proinflammatory capacity of 6-sulfo LacNAc (slan) DCs, representing a major subpopulation of human blood DCs.

METHODS:

SlanDCs were isolated from ECP-treated or untreated blood of healthy donors or GVHD patients by immunomagnetic isolation. The maturation of slanDC was determined by flow cytometry. Cytokine production of slanDCs was measured by enzyme-linked immunosorbent assay. SlanDC-mediated T-cell proliferation was evaluated by H-thymidine incorporation. SlanDC-mediated T-cell programming was determined by flow cytometry.

RESULTS:

ECP efficiently impairs the spontaneous maturation and secretion of proinflammatory tumor necrosis factor-alpha, interleukin-1beta, and interleukin-12 by slanDCs. Furthermore, ECP markedly inhibits slanDC-induced proliferation of CD4 and CD8 T cells and polarization of naïve CD4 T lymphocytes into Th1 cells.

CONCLUSIONS:

These novel findings indicate that ECP efficiently impairs the proinflammatory capacity of slanDCs, which may represent an important mechanism for the therapeutic efficiency of ECP in GVHD.

• Authors: Michael Gerner, Kristina Hölig, Rebekka Wehner, Senming Zhao, Knut Schäkel, Michael Philipp Bachmann, Ernst Peter Rieber, Martin Bornhäuser, Marc Schmitz
• Journal: Transplantation (Transplantation) Vol. 87 Issue 8 Pg. 1134-9 (Apr 27 2009) ISSN: 1534-6080 [Electronic] United States
• PMID: 19384158 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 6-sulfo-LacNac
• ABO Blood-Group System
• Amino Sugars
• Carrier Proteins
• Membrane Proteins
• PLVAP protein, human
• Platelet Endothelial Cell Adhesion Molecule-1
• Proteome
• von Willebrand Factor

Topics

• ABO Blood-Group System (analysis, immunology)
• Amino Sugars (analysis)
• Carrier Proteins (analysis, immunology)
• Dendritic Cells (physiology, radiation effects)
• Humans
• Immunoblotting
• Inflammation (physiopathology, prevention & control)
• Membrane Proteins (analysis, immunology)
• Photopheresis
• Platelet Endothelial Cell Adhesion Molecule-1 (analysis, immunology)
• Proteome
• von Willebrand Factor (analysis, immunology)