Extracorporeal photopheresis efficiently impairs the proinflammatory capacity of human 6-sulfo LacNAc dendritic cells.
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.
Gerner
Michael
M
Institute of Immunology, Medical Faculty, Technical University of Dresden, Dresden, Germany.
Hölig
Kristina
K
Wehner
Rebekka
R
Zhao
Senming
S
Schäkel
Knut
K
Bachmann
Michael Philipp
MP
Rieber
Ernst Peter
EP
Bornhäuser
Martin
M
Schmitz
Marc
M
D000017:ABO Blood-Group System / Q000032:analysis* / Q000276:immunology; D000606:Amino Sugars / Q000032:analysis*; D002352:Carrier Proteins / Q000032:analysis / Q000276:immunology; D003713:Dendritic Cells / Q000502:physiology* / Q000528:radiation effects; D006801:Humans; D015151:Immunoblotting; D007249:Inflammation / Q000503:physiopathology* / Q000517:prevention & control; D008565:Membrane Proteins / Q000032:analysis / Q000276:immunology; D017893:Photopheresis; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis / Q000276:immunology; D020543:Proteome; D014841:von Willebrand Factor / Q000032:analysis / Q000276:immunology
C467438:6-sulfo-LacNac; D000017:ABO Blood-Group System; D000606:Amino Sugars; D002352:Carrier Proteins; D008565:Membrane Proteins; C486771:PLVAP protein, human; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D020543:Proteome; D014841:von Willebrand Factor