TY  - JOUR
A1  - Landwehr-Kenzel, Sybille
A1  - Zobel, Anne
A1  - Hoffmann, Henrike
A1  - Landwehr, Niels
A1  - Schmueck-Henneresse, Michael
A1  - Schachtner, Thomas
A1  - Roemhild, Andy
A1  - Reinke, Petra
T1  - Ex vivo expanded natural regulatory T cells from patients with end-stage renal disease or kidney transplantation are useful for autologous cell therapy
JF  - Kidney international : official journal of the International Society of Nephrology
N2  - Novel concepts employing autologous, ex vivo expanded natural regulatory T cells (nTreg) for adoptive transfer has potential to prevent organ rejection after kidney transplantation. However, the impact of dialysis and maintenance immunosuppression on the nTreg phenotype and peripheral survival is not well understood, but essential when assessing patient eligibility. The current study investigates regulatory T-cells in dialysis and kidney transplanted patients and the feasibility of generating a clinically useful nTreg product from these patients. Heparinized blood from 200 individuals including healthy controls, dialysis patients with end stage renal disease and patients 1, 5, 10, 15, 20 years after kidney transplantation were analyzed. Differentiation and maturation of nTregs were studied by flow cytometry in order to compare dialysis patients and kidney transplanted patients under maintenance immunosuppression to healthy controls. CD127 expressing CD4(+)CD25(high)FoxP3(+) nTregs were detectable at increased frequencies in dialysis patients with no negative impact on the nTreg end product quality and therapeutic usefulness of the ex vivo expanded nTregs. Further, despite that immunosuppression mildly altered nTreg maturation, neither dialysis nor pharmacological immunosuppression or previous acute rejection episodes impeded nTreg survival in vivo. Accordingly, the generation of autologous, highly pure nTreg products is feasible and qualifies patients awaiting or having received allogenic kidney transplantation for adoptive nTreg therapy. Thus, our novel treatment approach may enable us to reduce the incidence of organ rejection and reduce the need of long-term immunosuppression.
KW  - adoptive T-cell transfer
KW  - autologous cell therapy
KW  - end-stage renal disease
KW  - kidney transplantation
KW  - regulatory T cells
Y1  - 2018
U6  - https://doi.org/10.1016/j.kint.2018.01.021
SN  - 0085-2538
SN  - 1523-1755
VL  - 93
IS  - 6
SP  - 1452
EP  - 1464
PB  - Elsevier
CY  - New York
ER  -