Ex vivo expanded natural regulatory T cells from patients with end-stage renal disease or kidney transplantation are useful for autologous cell therapy
| Autor: | Andy Roemhild, Niels Landwehr, Henrike Hoffmann, Thomas Schachtner, Sybille Landwehr-Kenzel, Petra Reinke, Anne Zobel, Michael Schmueck-Henneresse |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Adult
Male Department Psychologie 0301 basic medicine Adoptive cell transfer Time Factors Adolescent Cell Survival medicine.medical_treatment Cell Separation 030230 surgery T-Lymphocytes Regulatory Transplantation Autologous End stage renal disease Young Adult 03 medical and health sciences 0302 clinical medicine Renal Dialysis medicine Humans ddc:610 Interleukin-7 receptor Cells Cultured Kidney transplantation Dialysis Cell Proliferation Kidney business.industry Immunosuppression Middle Aged medicine.disease Adoptive Transfer Kidney Transplantation Transplant Recipients Cross-Sectional Studies Phenotype Treatment Outcome 030104 developmental biology medicine.anatomical_structure Nephrology Case-Control Studies Immunology Feasibility Studies Kidney Failure Chronic Female business Biomarkers Immunosuppressive Agents Ex vivo |
| Zdroj: | Kidney International. 93:1452-1464 |
| ISSN: | 0085-2538 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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