Purpose: Life-long use of immunosuppressants (IS) is associated with significant immunological and non-immunological adverse effects. Thus, minization, followed by complete cessation of IS has been an ultimate goal in organ transplantation. Peviously, we have shown that infusion of ex-vivo generated donor-antigen-specific regulatory T cells (Tregs) allowed early withdrawal of IS and induction of tolerance after renal transplantation in non-human primates. The present study was conducted to determine the safety and the efficacy of Treg-based cell therapy in living donor liver transplantation (LDLT).
Methods:The study was performed with 10 consecutive adult LDLTs. On the day before LDLT, Tregs were started to generate ex-vivo for 2 weeks by co-culturing recipient-PBMCs (+splenocytes) with irradiated donor-PMBCs under ΑCD80 + ΑCD86 mAbs. IS were with steroid+MMF+tacrolimus (TAC) or cyclosporine (CYA), while the former two were stopped within a month. Cyclophosphamide (40 mg/kg) was given on POD 5, and Tregs were infused on POD 13. TAC (or CYA) was maintained until 6 months, from when it was reduced every 2-3 months as follows; once daily, and thrice-, twice- and once-weekly, and finally stopped.
Results: All recipients, except for case 5, maintained good liver function during reduction and after cessation. Case 5 was replaced on regular IS and excluded from the study due to imappropriate generation of Tregs. No adverse events were seen in all patients. Two-week co-culture increased CD4+CD25+Foxp3+ (6.7±3.8% to 28.1%±7.7%) and CD4+CD127loFoxp3+ T cells (8.2±6.0% to 26.2±7.7%). Cultured cells inhibited MLR in a cell-number-dependent fashion.
Conclusion: Cell therapy based on ex-vivo generated donor-antigen specific Tregs allowed early reduction of IS in 9 cases and ultimate cessation in 3 cases after LDLT.
To cite this abstract in AMA style:Yamashita K, Zaitsu M, Nagatsu A, Goto R, Oura T, Watanabe M, Aoyagi T, Suzuki T, Shimamura T, Sato N, Sugita J, Hatanaka K, Taniguchi M, Furukawa H, Bashuda H, Okumura K, Todo S. Successful Reduction and Cessation of Immunosuppressants by a Regulatory T Cell-Based Cell Therapy in Living Donor Liver Transplantation: A Pilot Study for Tolerance Induction [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/successful-reduction-and-cessation-of-immunosuppressants-by-a-regulatory-t-cell-based-cell-therapy-in-living-donor-liver-transplantation-a-pilot-study-for-tolerance-induction/. Accessed May 7, 2021.
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