Wan Yun-Le, Zheng Shu-Sen, Jia Chang-Ku, Liang Ting-Bo, Huang Dong-Sheng, Wang Wei-Lin, Li Min-Wei, Zhao Zhi-Cheng
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.
Hepatobiliary Pancreat Dis Int. 2003 Feb;2(1):38-43.
To investigate the gene expression of 4-1BB in peripheral blood mononuclear cells (PBMCs) and its possible significance in clinical liver transplantation.
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.
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.
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.
研究4-1BB在人外周血单个核细胞(PBMCs)中的基因表达及其在临床肝移植中的可能意义。
采用逆转录聚合酶链反应(RT-PCR)检测22例肝移植患者、13例原发性肝癌(PLC)患者及12例健康对照者PBMCs中4-1BB的基因表达。为确定4-1BB分子是否也表达于CD4+和CD8+T细胞表面,采用流式细胞术分析肝移植患者血液中T细胞亚群的表型。
肝移植术后稳定存活者的PBMCs中可检测到4-1BB mRNA,而PLC患者及健康对照者的PBMCs中几乎未检测到。同时,健康对照者及PLC患者的CD4+和CD8+T细胞表面几乎不表达4-1BB。然而,肝移植术后稳定存活者的CD4+和CD8+T细胞表面可检测到低水平的4-1BB表达。
本研究表明,肝移植患者虽已稳定,但效应T细胞仍可通过4-1BB分子信号被激活,并对移植物产生持续的免疫反应。阻断4-1BB/4-1BBL通路可能有助于减少免疫抑制剂的临床用量并延长移植物存活时间。