Expression of 4-1BB molecule on peripheral blood T cells in liver transplanted patients and its clinical implication.
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.
Department of Hepatobiliary Pancreatic Surgery, Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China. wanyl036@hotmail.com
Yun-Le
YL
Wan
Shu-Sen
SS
Zheng
Chang-Ku
CK
Jia
Ting-Bo
TB
Liang
Dong-Sheng
DS
Huang
Wei-Lin
WL
Wang
Min-Wei
MW
Li
Zhi-Cheng
ZC
Zhao
D000328:Adult; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000276:immunology*; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9
D015703:Antigens, CD; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C505714:TNFRSF9 protein, human; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9