Effects of tacrolimus (FK506) and mycophenolate mofetil (MMF) on regulatory T cells and co-inhibitory receptors in the peripheral blood of human liver allograft patients.

Recent studies have shown that a combination treatment of mycophenolate mofetil (MMF) and tacrolimus (FK506) may be an option for organ transplantation patients. In this study, we detected the effects of FK506 and MMF on the expressions of regulatory T cells (Tregs) and co-inhibitory receptors on Tregs in peripheral blood mononuclear cells (PBMC) of patients with stable phase after liver transplantation. A total of 35 patients with stable stage after 6 months of liver transplantation were divided into two groups including 20 patients were treated with FK506 monotherapy (FK506 group), and 15 patients with FK506 and MMF combination (FK506 + MMF group). 15 healthy subjects were served as the control. It is found that percentages of CD3, CD3CD4 and CD3CD8 T cells in FK506 group are lowered compared to the control group but they are elevated in FK506 + MMF group. Amount of CD4CD25CD127low/-Treg cells in CD3 CD4T cells in FK506 + MMF group was higher than that in FK506 group and control group. The expressions of co-inhibitory receptors (CTLA-4, PD-1, Tim-3, LAG-3 and TIGIT) on Tregs in FK506 + MMF group were significant higher than those in the FK506 group and control group. The levels of the relative cytokines (TGF-β and IL-10) in FK506 group are down-regulated compared to the control group. The application of FK506 combined with MMF may be superior to FK506 monotherapy for the patients to further induce the immune tolerance after liver transplantation.