title: Extracorporeal photophoresis augments function of CD4+CD25+FoxP3+ regulatory T cells by triggering adenosine production.
abstract: BACKGROUND
  During extracorporeal photophoresis (ECP), peripheral blood mononuclear cells are treated with DNA-intercalating agents and irradiated with ultraviolet light. This procedure exerts immunosuppressive effects, most likely mediated by regulatory T cells (Treg). However, the underlying mechanisms are not clear yet. In our study, we investigated the effect of ECP on frequency and function of Treg in the peripheral blood of patients suffering from graft-versus-host disease.
  
  
  METHODS
  Whole blood samples from graft-versus-host disease patients were taken before and after the ECP treatment on 2 consecutive days. Phenotypical analysis of changes in distinct leukocyte subsets within the peripheral blood of patients and healthy controls was performed by means of flow cytometry. Functional analysis of the Treg population after magnetic bead isolation was performed using conventional suppression assays, and adenosine was detected by means of high pressure liquid chromatography and Lanzetta assays.
  
  
  RESULTS
  We show that the frequency of CD4/CD25/FoxP3 Treg in the peripheral blood increases after each cycle of ECP and also in the course of treatment. The suppressive capacity of Treg after ECP was increased compared with that of Treg before ECP, although not reaching the suppression levels obtained with Treg from healthy controls. Furthermore, we show that ECP stimulates the CD39-mediated production of adenosine by Treg, which substantially reduces the T-cell proliferation in in vitro suppression assays.
  
  
  CONCLUSIONS
  Our data indicate that ECP stimulates the conversion of ATP to adenosine by the ectonucleotiodase CD39, which acts as a novel soluble immunosuppressive reagent mediating immunosuppression of Treg.
authors: Department of Dermatology, University Hospital Heidelberg, Vosstrasse 11, Heidelberg, Germany.
authors: Sabrina
authors: S
authors: Schmitt
authors: Theron S
authors: TS
authors: Johnson
authors: Svetlana
authors: S
authors: Karakhanova
authors: Helmut
authors: H
authors: Näher
authors: Karsten
authors: K
authors: Mahnke
authors: Alexander H
authors: AH
authors: Enk
mesh_terms: D000241:Adenosine / Q000378:metabolism*; D015703:Antigens, CD / Q000032:analysis; D001081:Apyrase / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016022:Case-Control Studies; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis*; D006086:Graft vs Host Disease / Q000276:immunology / Q000628:therapy*; D006801:Humans; D016130:Immunophenotyping; D007165:Immunosuppression Therapy / Q000379:methods*; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis*; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008213:Lymphocyte Activation; D008297:Male; D017893:Photopheresis; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D013997:Time Factors
chemical_list: D015703:Antigens, CD; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D018950:Lipopolysaccharide Receptors; D001081:Apyrase; C067869:CD39 antigen; D000241:Adenosine