OBJECTIVE: To investigate the gene expression of 4-1BB in peripheral blood mononuclear cells (PBMCs) and its possible significance in clinical liver transplantation.
METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the gene expression of 4-1BB in PBMCs from 22 patients receiving liver transplantation, 13 patients with primary liver carcinoma (PLC), and 12 healthy controls. To determine whether 4-1BB molecule is also expressed on the surface of CD4+ and CD8+ T cell, flow cytometry was used to analyse the phenotype of T cell subsets from the blood of liver transplantation patients.
RESULTS: 4-1BB mRNA was detected in PBMCs from stable survivors after liver transplantation, but almost not detected in PBMCs from PLC patients and healthy controls. Meanwhile, 4-1BB was almost not expressed on the surface of CD4+ and CD8+ T cells in healthy controls and PLC patients. A low level of 4-1BB expression, however, was found on the surface of CD4+ and CD8+ T cells from the stable survivors after liver transplantation.
CONCLUSIONS: This study demonstrates that although patients are stable after liver transplantation, effector T-cells can also be activated through the signal of 4-1BB molecule and persistent immune response to grafts. Blockage of 4-1BB/4-1BBL pathway may benefitially reduce the clinical dosage of immunosuppressive agents and prolong the survival of grafts.