To investigate the value of apoptosis of the allo antigen specific T cells induced by Fas/FasL pathway in preventing graft versus host disease (GVHD), the CD34 + cells transfected with FasL or not, used as stimul...To investigate the value of apoptosis of the allo antigen specific T cells induced by Fas/FasL pathway in preventing graft versus host disease (GVHD), the CD34 + cells transfected with FasL or not, used as stimulus cells, were mixed with allo antigen specific T lymphocytes in presence or absence of IFN γand IL 2. After 5 days, apoptosis of T cells was detected by TdT nick end mediated dUTP labeling (TUNEL) and flow cytometry (FCM). The affects of these two cytokines on CD34 + cells in the graft were also compared. The ratio of apoptosis of T cells was 12.1±1.5 % when CD34 + cells transfected with FasL was used as stimulus cells, much higher than that of CD34 + cells non transfected (3.2 ±1.1 %, P <0.01). And in presence of IFN γ or IL 2, the ratio reached 20.1±2.3 %, 17.6±1.3 % respectively ( P <0.01). However, IFN γ up regulated Fas expression of CD34 + cells and increased the sensibility of CD34 + cells to soluble FasL(sFasL); IL 2 showed no such affect. It is possible to induce apoptosis of the allo antigen specific T cells of grafts activated by allo antigen by exogenous Fas ligand expressed on recipient cells and this might provide a new approach for preventing GVHD and IL 2 may be more suitable for clinical application.展开更多
Objective: To investigate whether apoptotic cell death is involved in liver xenograft rejection and the molec- ular mechanism of apoptosis. Methods: After hamster-to-rat orthotopic liver trans- plantation, apoptosis i...Objective: To investigate whether apoptotic cell death is involved in liver xenograft rejection and the molec- ular mechanism of apoptosis. Methods: After hamster-to-rat orthotopic liver trans- plantation, apoptosis in the xenograft was observed histologically and by in situ end-labelling of fragmen- ted DNA. CD_8 antigen, perforin, Fas-L and TGF-β_1 were observed immunohistochemically in the graft. Results: In xenogenic rejection, OX_8 (CD_8) positive T lymphocyte was observed on day 2 post-transplan- tation, evidently on day 5. The expression of perfor- in and Fas-L in grafts occurred on day 4 post-trans- plantation, and it was more evident in the rejection. In control group, the lymphocyte was rarely seen, and the expression of Fas-L and perforin was not found. Both xenogeneic and syngeneic grafts showed the expression of TGF-β_1 on the first day after trans- plantation. The expression of TGF-β_1, however, in- creased subsequently in the xenogeneic graft in con- trast to its normalization in the syngeneic graft. In the xenogeneic graft, apoptosis occurred on day 1 af- ter transplantation, decreased on day 2, increased on day 3, and peaked on day 5. Apoptosis was similar in the syngeneic and xenogeneic grafts on day 1 after transplantation, but decreased to normal one day lat- er. The more severe apoptosis, the more severe acute rejection, and the more evident expression of perfor- in, Fas-L and TGF-β_1. Conclusion: Apoptosis as a mechanism of cell death exists in the acute rejection of liver xenograft, and it is related closely to the expression of perforin, TGF- β_1 and Fas-L.展开更多
Hepatitis C virus(HCV)infection affects about 170 million people worldwide and it is a major cause of liver cirrhosis and hepatocellular carcinoma.HCV is a hepatotropic non-cytopathic virus able to persist in a great ...Hepatitis C virus(HCV)infection affects about 170 million people worldwide and it is a major cause of liver cirrhosis and hepatocellular carcinoma.HCV is a hepatotropic non-cytopathic virus able to persist in a great percentage of infected hosts due to its ability to escape from the immune control.Liver damage and disease progression during HCV infection are driven by both viral and host factors.Specifically,adaptive immune response carries out an essential task in controllingnon-cytopathic viruses because of its ability to recognize infected cells and to destroy them by cytopathic mechanisms and to eliminate the virus by non-cytolytic machinery.HCV is able to impair this response by several means such as developing escape mutations in neutralizing antibodies and in T cell receptor viral epitope recognition sites and inducing HCV-specific cytotoxic T cell anergy and deletion.To impair HCV-specific T cell reactivity,HCV affects effector T cell regulation by modulating T helper and Treg response and by impairing the balance between positive and negative co-stimulatory molecules and between pro-and antiapoptotic proteins.In this review,the role of adaptive immune response in controlling HCV infection and the HCV mechanisms to evade this response are reviewed.展开更多
基金hisprojectwassupportedbythegrantfromNationalNaturalScienceFoundationofChina (No .39770 76 7)
文摘To investigate the value of apoptosis of the allo antigen specific T cells induced by Fas/FasL pathway in preventing graft versus host disease (GVHD), the CD34 + cells transfected with FasL or not, used as stimulus cells, were mixed with allo antigen specific T lymphocytes in presence or absence of IFN γand IL 2. After 5 days, apoptosis of T cells was detected by TdT nick end mediated dUTP labeling (TUNEL) and flow cytometry (FCM). The affects of these two cytokines on CD34 + cells in the graft were also compared. The ratio of apoptosis of T cells was 12.1±1.5 % when CD34 + cells transfected with FasL was used as stimulus cells, much higher than that of CD34 + cells non transfected (3.2 ±1.1 %, P <0.01). And in presence of IFN γ or IL 2, the ratio reached 20.1±2.3 %, 17.6±1.3 % respectively ( P <0.01). However, IFN γ up regulated Fas expression of CD34 + cells and increased the sensibility of CD34 + cells to soluble FasL(sFasL); IL 2 showed no such affect. It is possible to induce apoptosis of the allo antigen specific T cells of grafts activated by allo antigen by exogenous Fas ligand expressed on recipient cells and this might provide a new approach for preventing GVHD and IL 2 may be more suitable for clinical application.
文摘Objective: To investigate whether apoptotic cell death is involved in liver xenograft rejection and the molec- ular mechanism of apoptosis. Methods: After hamster-to-rat orthotopic liver trans- plantation, apoptosis in the xenograft was observed histologically and by in situ end-labelling of fragmen- ted DNA. CD_8 antigen, perforin, Fas-L and TGF-β_1 were observed immunohistochemically in the graft. Results: In xenogenic rejection, OX_8 (CD_8) positive T lymphocyte was observed on day 2 post-transplan- tation, evidently on day 5. The expression of perfor- in and Fas-L in grafts occurred on day 4 post-trans- plantation, and it was more evident in the rejection. In control group, the lymphocyte was rarely seen, and the expression of Fas-L and perforin was not found. Both xenogeneic and syngeneic grafts showed the expression of TGF-β_1 on the first day after trans- plantation. The expression of TGF-β_1, however, in- creased subsequently in the xenogeneic graft in con- trast to its normalization in the syngeneic graft. In the xenogeneic graft, apoptosis occurred on day 1 af- ter transplantation, decreased on day 2, increased on day 3, and peaked on day 5. Apoptosis was similar in the syngeneic and xenogeneic grafts on day 1 after transplantation, but decreased to normal one day lat- er. The more severe apoptosis, the more severe acute rejection, and the more evident expression of perfor- in, Fas-L and TGF-β_1. Conclusion: Apoptosis as a mechanism of cell death exists in the acute rejection of liver xenograft, and it is related closely to the expression of perforin, TGF- β_1 and Fas-L.
基金Grants from"Instituto de Salud Carlos Ⅲ",Spain and"European Regional Development Fund(ERDF),a way of making Europe",E.U.,No.PI12/00130"Fundacion de In-vestigacion Medica Mutua Madrilena",Spain,No.8922/2011Lokhande MU was funded by a research grant from"Asoci-acion de Hepatologia Translacional"No.AHT-2010/01,Spain
文摘Hepatitis C virus(HCV)infection affects about 170 million people worldwide and it is a major cause of liver cirrhosis and hepatocellular carcinoma.HCV is a hepatotropic non-cytopathic virus able to persist in a great percentage of infected hosts due to its ability to escape from the immune control.Liver damage and disease progression during HCV infection are driven by both viral and host factors.Specifically,adaptive immune response carries out an essential task in controllingnon-cytopathic viruses because of its ability to recognize infected cells and to destroy them by cytopathic mechanisms and to eliminate the virus by non-cytolytic machinery.HCV is able to impair this response by several means such as developing escape mutations in neutralizing antibodies and in T cell receptor viral epitope recognition sites and inducing HCV-specific cytotoxic T cell anergy and deletion.To impair HCV-specific T cell reactivity,HCV affects effector T cell regulation by modulating T helper and Treg response and by impairing the balance between positive and negative co-stimulatory molecules and between pro-and antiapoptotic proteins.In this review,the role of adaptive immune response in controlling HCV infection and the HCV mechanisms to evade this response are reviewed.
