Liver transplantation is an established therapy for end-stage liver diseases. Graft rejection occurs unless the recipient receives immunosuppression after transplantation. This study aimed to explore the mechanism of ...Liver transplantation is an established therapy for end-stage liver diseases. Graft rejection occurs unless the recipient receives immunosuppression after transplantation. This study aimed to explore the mechanism of acute rejection of liver allografts in rats pre-treated with total body irradiation to eliminate passenger lymphocytes and to define the role of CD4＋CD25＋ regulatory T cells in the induction of immunotolerance in the recipient. Male Lewis rats were used as donors and male DA rats were re- cipients. Rats were randomly assigned to the following four groups： control group, homogeneity liver transplantation group, idio-immunotolerance group and acute rejection group. After transplantation, the survival time of each group, serum alanine aminotransferase, total bilirubin levels, number of Foxp3＋CD4＋CD25＋ regulatory T cells, expression of glucocorticoid-induced tumor necrosis factor receptor on T cell subgroups, histopathology of the hepatic graft and spleen cytotoxic T lymphocyte lytic activity were measured. In the acute rejection group, where donors were preconditioned with total body in＇adiation before liver transplantation, all recipients died between day 17 and day 21. On day 14, serum alanine aminotransferase increased signifi- cantly to （459.2±76.9） U L^- 1, total bilirubin increased to （124.1±33.7） μmol L-1 （P〈0.05） and the ratio of Foxp3＋CD4＋CD25＋ regulatory T cells decreased significantly to 1.50%±0.50% （P〈0.05） compared with the other groups. Analysis of the T cell subpopulations in the acute rejection group varied from the other groups. Histological analysis showed typical changes of acute rejection in the acute rejection group only. Preconditioning of the donors with total body irradiation eliminated passenger lymphocytes of the liver graft, and thus affected the course of tolerance and induced acute rejection after liver transplantation.展开更多
Reduced cellular immune function in patients after liver transplantation easily results in many types of viral infections,such as Epstein-Barr virus.Epstein-Barr virus is a γ-herpesvirus and is related to many malign...Reduced cellular immune function in patients after liver transplantation easily results in many types of viral infections,such as Epstein-Barr virus.Epstein-Barr virus is a γ-herpesvirus and is related to many malignant diseases,especially epithelial and lymph tumors.The abnormal interaction of cluster of differentiation 40 with cluster of differentiation 40 ligand and expression of cluster of differentiation 40 ligand are considered closely related to the development of myeloma cells.This study explored the influence and mechanism of Epstein-Barr virus infection on the phenotype and biological behavior of myeloma cells after liver transplantation.Flow cytometry was used to detect coexpression of cluster of differentiation 40 and cluster of differentiation 40 ligand in 10 samples of freshly isolated multiple myeloma cells.Cluster of differentiation 40 and cluster of differentiation 40 ligand were coexpressed in sample Nos.5,8,9,and 10,particularly in sample No.5.Western blot analysis was used to detect the expression of the Epstein-Barr virus antigens latent membrane protein 1 and Epstein-Barr virus nuclear antigen 2 in the multiple myeloma cell line RPMI 8226 infected with Epstein-Barr virus.The antigen expression indicated that Epstein-Barr virus can infect multiple myeloma virus cells in vitro.Reverse transcription-polymerase chain reaction revealed upregulated expression of cluster of differentiation 40 ligand on the infected RPMI 8226 cells,which may be involved in the anti-apoptosis activity of the infected cells.Confocal microscopy showed that pairs of molecules of cluster of differentiation 40,cluster of differentiation 40 ligand,and latent membrane protein 1 were colocalized on the surface of the infected cells.CXC chemokine receptor 4 was upregulated on the RPMI 8226 cells after Epstein-Barr virus infection.The migratory ability of the infected cells improved in the presence of the chemokine stromal cell-derived factor-1α.Anti-apoptosis and migration are known important biological characteristics of malignant cells.Our results indicate the involvement of Epstein-Barr virus in the origin and development of multiple myeloma.The risk of multiple myeloma increases when Epstein-Barr virus infects B cells in the germinal center,which may result in an anti-apoptosis effect of B cells and an improved ability to migrate from the germinal center to peripheral blood.展开更多
基金supported by the National Natural Science Foundation of China (Grant No. 61141013)the Key Medical Talents of Jiangsu Province(Grant No. RC2011090)+1 种基金the Natural Science Foundation of Jiangsu Province (Grant No. SBK201120268)the 333 Program for High Level Talents of Jiangsu Province (Grant No. 2011III-2640)
文摘Liver transplantation is an established therapy for end-stage liver diseases. Graft rejection occurs unless the recipient receives immunosuppression after transplantation. This study aimed to explore the mechanism of acute rejection of liver allografts in rats pre-treated with total body irradiation to eliminate passenger lymphocytes and to define the role of CD4＋CD25＋ regulatory T cells in the induction of immunotolerance in the recipient. Male Lewis rats were used as donors and male DA rats were re- cipients. Rats were randomly assigned to the following four groups： control group, homogeneity liver transplantation group, idio-immunotolerance group and acute rejection group. After transplantation, the survival time of each group, serum alanine aminotransferase, total bilirubin levels, number of Foxp3＋CD4＋CD25＋ regulatory T cells, expression of glucocorticoid-induced tumor necrosis factor receptor on T cell subgroups, histopathology of the hepatic graft and spleen cytotoxic T lymphocyte lytic activity were measured. In the acute rejection group, where donors were preconditioned with total body in＇adiation before liver transplantation, all recipients died between day 17 and day 21. On day 14, serum alanine aminotransferase increased signifi- cantly to （459.2±76.9） U L^- 1, total bilirubin increased to （124.1±33.7） μmol L-1 （P〈0.05） and the ratio of Foxp3＋CD4＋CD25＋ regulatory T cells decreased significantly to 1.50%±0.50% （P〈0.05） compared with the other groups. Analysis of the T cell subpopulations in the acute rejection group varied from the other groups. Histological analysis showed typical changes of acute rejection in the acute rejection group only. Preconditioning of the donors with total body irradiation eliminated passenger lymphocytes of the liver graft, and thus affected the course of tolerance and induced acute rejection after liver transplantation.
基金supported by the National Natural Science Foundation of China (Grant No. 61141013)the Key Medical Talents of Jiangsu Province(Grant No. RC2011090)+1 种基金the Natural Science Foundation of Jiangsu Province (Grant No. SBK201120268)the 333 Program for High-level Talents of Jiangsu Province (Grant No. 2011 III-2640)
文摘Reduced cellular immune function in patients after liver transplantation easily results in many types of viral infections,such as Epstein-Barr virus.Epstein-Barr virus is a γ-herpesvirus and is related to many malignant diseases,especially epithelial and lymph tumors.The abnormal interaction of cluster of differentiation 40 with cluster of differentiation 40 ligand and expression of cluster of differentiation 40 ligand are considered closely related to the development of myeloma cells.This study explored the influence and mechanism of Epstein-Barr virus infection on the phenotype and biological behavior of myeloma cells after liver transplantation.Flow cytometry was used to detect coexpression of cluster of differentiation 40 and cluster of differentiation 40 ligand in 10 samples of freshly isolated multiple myeloma cells.Cluster of differentiation 40 and cluster of differentiation 40 ligand were coexpressed in sample Nos.5,8,9,and 10,particularly in sample No.5.Western blot analysis was used to detect the expression of the Epstein-Barr virus antigens latent membrane protein 1 and Epstein-Barr virus nuclear antigen 2 in the multiple myeloma cell line RPMI 8226 infected with Epstein-Barr virus.The antigen expression indicated that Epstein-Barr virus can infect multiple myeloma virus cells in vitro.Reverse transcription-polymerase chain reaction revealed upregulated expression of cluster of differentiation 40 ligand on the infected RPMI 8226 cells,which may be involved in the anti-apoptosis activity of the infected cells.Confocal microscopy showed that pairs of molecules of cluster of differentiation 40,cluster of differentiation 40 ligand,and latent membrane protein 1 were colocalized on the surface of the infected cells.CXC chemokine receptor 4 was upregulated on the RPMI 8226 cells after Epstein-Barr virus infection.The migratory ability of the infected cells improved in the presence of the chemokine stromal cell-derived factor-1α.Anti-apoptosis and migration are known important biological characteristics of malignant cells.Our results indicate the involvement of Epstein-Barr virus in the origin and development of multiple myeloma.The risk of multiple myeloma increases when Epstein-Barr virus infects B cells in the germinal center,which may result in an anti-apoptosis effect of B cells and an improved ability to migrate from the germinal center to peripheral blood.
