Background: Liver transplantation (LT) has become an accepted modality for the treatment of patients with end-stage liver failure. However, a life-long intake of immunosuppressants (IS) to prevent rejection always accompanies immunological and non-immunological risks. Freedom of the recipients from these problems, e.g. Operational Tolerance (OT), has been an ultimate goal in LT.

Objects: To determine whether a regulatory T cell (Treg)-based cell therapy afford OT in living donor LT (LDLT).

Materials and Methods: Consecutive 10 adult patients underwent LDLT. Indications were HCV, HCC, alcohol, PBC, PSC and NASH. Peripheral blood mononuclear cells (PBMNs) were collected from both donor and recipient by leukapheresis and Tregs were expanded ex vivo by a 2-week culture of recipient PBMNs with irradiated donor PBMNs under the presence of anti-CD80/anti-CD86 mAbs. They were infused into the recipient on postoperative day (POD) 13. Cyclophosphmide (CP) was given on POD5, and steroids and MMF were stopped within one month, while the patients were left on culcineurin inhibitor (CI) monotherapy. At 6 months after LDLT, when graft function and histology were normal, CI was gradually tapered by spaced doses until it was discontinued 12 months later.

Results: Results were shown below. Of the 10 recipients, 5 are free from IS for 1 month to 10 months, 3 are under smooth weaning processes, and the other 2 resume low dose CI monotherapy. All of them have normal liver function without histological evidence of rejection. Of the expanded cells by the culture, Tregs were found as a major cell type with suppressive function. Although they were supposed to have specificity against donor antigen, serial tests of mixed lymphocyte reaction (MLR) using recipient PBMNs revealed no consistency, indicating OT by Treg suppression is not systemic event, rather it is local.

Conclusion: A preliminary results of our experience suggest that OT in LT is approaching a clinical reality by a Treg-based cell therapy. The protocol is safe and promising not only in LDLT but also for diseased donor LT.