Role of Dendritic Cells in the Context of Acute Cellular Rejection: Comparison Between Tacrolimus- or Cyclosporine A-Treated Heart Transplanted Recipients

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. (C) 2014 International Clinical Cytometry Society