*Purpose: A sequential clinical trial of autologous polyclonal T regulatory cellular therapy compared with a standardised reference cohort of live donor kidney transplant recipients. The objective was to demonstrate feasibility, safety, risk of rejection and potential minimisation of immunosuppression in the T regulatory cell therapy treated cohort.

*Methods: Living donor transplant recipients receiving their first kidney transplant with moderate sensitisation status (PRA<40%) were recruited in 2 sequential clinical trials to form an initial reference and subsequent cell therapy cohort. All received immunosuppression with Mycophenolate mofetil (MMF), Tacrolimus and tapered steroids. Induction therapy with Basiliximab was only used in the reference group. Polyclonal T regulatory cells were isolated from 350ml of whole blood from transplant recipients in the cell therapy group 4-6 weeks before transplantation and expanded in culture in a dose escalation format to produce 1 -10 x10⁶ cells per kg for infusion at Day 5 post-transplantation. Recipients had a protocol biopsy at month 7 and the opportunity of MMF withdrawal. Follow up was continued for 4 years.

*Results: 19[median age 46(31-57) yrs; 74% male; 79% white] transplant recipients in the reference group and 12[median age 44(28-69) yrs; 92% male; 83% white] in the cell therapy group. Similar HLA mismatches in both groups: 1-2 mismatches 47% v 42%; 3-4 mismatches 42% v 50%; 5-6 mismatches 11% v8 % reference v cell therapy groups. Patient and Transplant survival 100% in both groups; acute rejection free survival at 1 and 4 years post transplant respectively 84% v 100% and 78.9% v 100% in reference and cell therapy groups. There were no adverse reactions related to T regulatory cell infusions and reduced BK virus and CMV infection rates in the cell therapy cohort. Four patients in the cell therapy group had MMF withdrawn at 7 months post transplant and remain rejection free on Tacrolimus monotherapy 4 years post transplant.

*Conclusions: This study demonstrates the safety of infusion of autologous polyclonal T regulatory cells as an adjuvant to immunosuppressive therapy in kidney transplantation. The reduced incidence of viral infection and absence of malignancy during the extended follow-up to 4 years post cell infusion is very reassuring. Successful transplantation without induction therapy and tapering to monotherapy with Tacolimus in 33% of the T regulatory cell therapy group is a potentially promising means of immunosuppression minimalisation and requires testing in large randomised clinical trials

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