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

Abstract

Context: Recent studies have shown that a combination treatment of mycophenolate mofetil (MMF) and tacrolimus (FK506) may be an option for organ transplantation patients.

Objective: 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.

Materials and methods: 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.

Results: It is found that percentages of CD3⁺, CD3⁺CD4⁺ and CD3⁺CD8⁺ T cells in FK506 group are lowered compared to the control group but they are elevated in FK506 + MMF group. Amount of CD4⁺CD25⁺CD127low/-Treg cells in CD3⁺ CD4⁺T 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.

Conclusion: 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.

Keywords:

• Tacrolimus
• mycophenolate mofetil
• regulatory T cells
• peripheral blood mononuclear cells
• co-inhibitory receptors
• liver transplantation

Disclosure statement

No potential conflict of interest was reported by the authors.