title: Role of dendritic cells in the context of acute cellular rejection: comparison between tacrolimus- or cyclosporine A-treated heart transplanted recipients.
abstract: BACKGROUND
  In the last years many studies have been designed to predict risk of acute rejection and to adapt the immunosuppressive therapy. The importance of dendritic cells (DCs) in the immune response, especially their role in tolerance is known. Thus, we investigated the influence of tacrolimus (TAC)-based and of cyclosporine A (CsA)-based immunosuppressive therapies on dendritic cells and the incidence of rejection in heart transplant recipients.
  
  
  METHODS
  Groups consisted of 14 CsA treated and 15 TAC treated patients. At different study time points (0, 3 and 6 months after study begin) peripheral blood from the patients was drawn to analyse (1) blood concentration of CsA or TAC (trough value) and (2) percentages of plasmacytoid and myeloid DC (p and mDC) subsets using flow cytometry. Histological rejection grading was performed of endomyocardial biopsies.
  
  
  RESULTS
  TAC treated patients had significantly higher values of pDCs (CsA group 53.9%±13.0%; TAC group 67.5%±8.4%; p<0.05) and significantly lower values of mDCs than CsA treated patients (CsA group 58%±19.0%; TAC group 45.2%±10.7%; p<0.05). In general, HTx patients with rejection grade of ≥2 had significant lower values of pDCs (55.1%±16.2%) compared to patients without rejection (63.6%±10.5%; p<0.05). TAC-treated patients had significantly less rejections CsA-treated patients (CsA group 0.86±0.95; TAC group 0.2±0.4; p<0.05).
  
  
  CONCLUSIONS
  Our results showed that HTx patients with high pDCs had a lower risk for rejection and that TAC-treated patients had higher pDCs values compared to CsA-treated patients. Future studies need to define individual pDC values to predict acute cellular rejection.
authors.affiliation: University Leipzig, Department of Cardiac Surgery, Heart Center, Leipzig, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: John
authors.forename: Maja-Theresa
authors.initials: MT
authors.lastname: Dieterlen
authors.forename: Attila
authors.initials: A
authors.lastname: Tarnok
authors.forename: Jens
authors.initials: J
authors.lastname: Garbade
authors.forename: Hartmuth B
authors.initials: HB
authors.lastname: Bittner
authors.forename: Friedrich W
authors.initials: FW
authors.lastname: Mohr
authors.forename: Markus J
authors.initials: MJ
authors.lastname: Barten
mesh_terms: D002452:Cell Count; D016572:Cyclosporine / Q000097:blood / Q000627:therapeutic use*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006084:Graft Rejection / Q000276:immunology*; D016027:Heart Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016559:Tacrolimus / Q000097:blood / Q000627:therapeutic use*
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus
keywords: acute cellular rejection; biomarker; dendritic cells; flow cytometry; heart transplantation