免疫耐受是器官移植临床研究的终极目标,是改善移植患者预后生存的关键。调节性T细胞(regulatory T cells,Tregs)在诱导免疫耐受过程中发挥着重要作用,如何诱导供体产生特异性Tregs是诱导免疫耐受突破的关键。尽管近20年来已经证实CD8^+...免疫耐受是器官移植临床研究的终极目标,是改善移植患者预后生存的关键。调节性T细胞(regulatory T cells,Tregs)在诱导免疫耐受过程中发挥着重要作用,如何诱导供体产生特异性Tregs是诱导免疫耐受突破的关键。尽管近20年来已经证实CD8^+Tregs在移植诱导免疫耐受中发挥重要的作用,但其特性仍然存在很大的争议。本文拟对CD8^+Tregs移植免疫耐受研究进展作一综述,探讨其在诱导肝移植免疫耐受中的潜力。展开更多
AIM： To report a retrospective analysis of preliminary results of 36 patients who received sirolimus （SRL, Rapamune, rapamycin） in a consecutive cohort of 248 liver allograft recipients. METHODS： Thirty-six liver ...AIM： To report a retrospective analysis of preliminary results of 36 patients who received sirolimus （SRL, Rapamune, rapamycin） in a consecutive cohort of 248 liver allograft recipients. METHODS： Thirty-six liver transplant patients with hepatocellular carcinoma （HCC） who were switched to SRL- based immunosuppression therapy from tacrolimus were enrolled in this study. The patients who were diagnosed as advanced HCC before orthotopic liver transplantation （OLT） were divided into group A （n = 11）, those who were found to have HCC recurrence and/or metastasis after OLT were assigned to group B （n = 18）, and those who developed renal insuffidency caused by caldneurin inhibitor （CNI） were assigned to group C （n = 7） after OLT. RESULTS： The patients were followed up for a median of 10.4 mo （range, 3.8-19.1 mo） after conversion to SRL therapy and 12.3 mo （range, 5.1-34.4 too） after OLT. Three patients developed mild acute cellular rejection 2 wk after initiating SRL therapy, which was fully reversed after prednisolone pulse therapy. In group A, only 1 patient was found to have HCC recurrence and metastasis 12 mo after OLT. In group B, 66.7% （12/18） patients （2 with progressive tumor, 7 with stable tumor and 3 without tumor） were still alive due to conversing to SRL and/ or resection for HCC recurrence at the end of a median follow-up of 6.8 mo post conversion and 10.7 mo posttransplant. In group C, no HCC recurrence was demonstrated in 7 patients, and renal function became normal after SRL therapy. Thrombocytopenia （n = 2）, anemia （n = 8）, and oral aphthous ulcers （n = 7） found in our cohort were easily manageable. CONCLUSION： The conversion to SRL-based immunosuppression may inhibit the recurrence and metastasis of HCC and improve CNI-induced renal insufficiency in OLT patients with HCC.展开更多
Mesenchymal stem cells （MSCs） have great potential for treating various diseases, especially those related to tissue damage involving immune reactions. Various studies have demonstrated that MSCs are strongly immuno...Mesenchymal stem cells （MSCs） have great potential for treating various diseases, especially those related to tissue damage involving immune reactions. Various studies have demonstrated that MSCs are strongly immunosuppressive in vitro and in vivo. Our recent studies have shown that un-stimulated MSCs are indeed incapable of immunosuppression; they become potently immunosuppressive upon stimulation with the supernatant of activated lymphocytes, or with combinations of IFN-γ, with TNF-α, IL-1α or IL-1β. This observation revealed that under certain circumstances, inflammatory cytokines can actually become immunosuppressive. We showed that there is a species variation in the mechanisms of MSC-mediated immunosuppression： immunosuppression by cytokine-primed mouse MSCs is mediated by nitric oxide （NO）, whereas immunosuppression by cytokine-primed human MSCs is executed through indoleamine 2, 3-dioxygenase （IDO）. Additionally, upon stimulation with the inflammatory cytokines, both mouse and human MSCs secrete several leukocyte chemokines that apparently serve to attract immune cells into the proximity with MSCs, where NO or IDO is predicted to be most active. Therefore, immunosuppression by inflammatory cytokine-stimulated MSCs occurs via the concerted action of chemokines and immune-inhibitory NO or IDO produced by MSCs. Thus, our results provide novel information about the mechanisms of MSC-mediated immunosuppression and for better application of MSCs in treating tissue injuries induced by immune responses.展开更多
We used a potent and specific monoclonal antibody to somatostatin to test the physiologic inhibitory role of the tetradecapeptide somatostatin on pancreatic secretion.Somatostatin immunoneutralization increased both t...We used a potent and specific monoclonal antibody to somatostatin to test the physiologic inhibitory role of the tetradecapeptide somatostatin on pancreatic secretion.Somatostatin immunoneutralization increased both the total amylase and volume of pancreatic secretion.Cholecystokinin-A receptor antagonism abolished the stimulatory effect of somatostatin immunoneutralization.We conclude that somatostatin tonically inhibits pancreatic secretion in fasted rats via inhibition of the release or action of cholecystokinin.Furthermore,the source of these peptides is likely islet delta cells and intrapancreatic neurons,respectively.展开更多
文摘免疫耐受是器官移植临床研究的终极目标,是改善移植患者预后生存的关键。调节性T细胞(regulatory T cells,Tregs)在诱导免疫耐受过程中发挥着重要作用,如何诱导供体产生特异性Tregs是诱导免疫耐受突破的关键。尽管近20年来已经证实CD8^+Tregs在移植诱导免疫耐受中发挥重要的作用,但其特性仍然存在很大的争议。本文拟对CD8^+Tregs移植免疫耐受研究进展作一综述,探讨其在诱导肝移植免疫耐受中的潜力。
基金Supported by the key project grant of the Science and Technological Committee of Shanghai Municipality, No.024001119the Foundation for "New Star of Medicine" of Shanghai Health Bureau, No. 1999-59
文摘AIM： To report a retrospective analysis of preliminary results of 36 patients who received sirolimus （SRL, Rapamune, rapamycin） in a consecutive cohort of 248 liver allograft recipients. METHODS： Thirty-six liver transplant patients with hepatocellular carcinoma （HCC） who were switched to SRL- based immunosuppression therapy from tacrolimus were enrolled in this study. The patients who were diagnosed as advanced HCC before orthotopic liver transplantation （OLT） were divided into group A （n = 11）, those who were found to have HCC recurrence and/or metastasis after OLT were assigned to group B （n = 18）, and those who developed renal insuffidency caused by caldneurin inhibitor （CNI） were assigned to group C （n = 7） after OLT. RESULTS： The patients were followed up for a median of 10.4 mo （range, 3.8-19.1 mo） after conversion to SRL therapy and 12.3 mo （range, 5.1-34.4 too） after OLT. Three patients developed mild acute cellular rejection 2 wk after initiating SRL therapy, which was fully reversed after prednisolone pulse therapy. In group A, only 1 patient was found to have HCC recurrence and metastasis 12 mo after OLT. In group B, 66.7% （12/18） patients （2 with progressive tumor, 7 with stable tumor and 3 without tumor） were still alive due to conversing to SRL and/ or resection for HCC recurrence at the end of a median follow-up of 6.8 mo post conversion and 10.7 mo posttransplant. In group C, no HCC recurrence was demonstrated in 7 patients, and renal function became normal after SRL therapy. Thrombocytopenia （n = 2）, anemia （n = 8）, and oral aphthous ulcers （n = 7） found in our cohort were easily manageable. CONCLUSION： The conversion to SRL-based immunosuppression may inhibit the recurrence and metastasis of HCC and improve CNI-induced renal insufficiency in OLT patients with HCC.
文摘Mesenchymal stem cells （MSCs） have great potential for treating various diseases, especially those related to tissue damage involving immune reactions. Various studies have demonstrated that MSCs are strongly immunosuppressive in vitro and in vivo. Our recent studies have shown that un-stimulated MSCs are indeed incapable of immunosuppression; they become potently immunosuppressive upon stimulation with the supernatant of activated lymphocytes, or with combinations of IFN-γ, with TNF-α, IL-1α or IL-1β. This observation revealed that under certain circumstances, inflammatory cytokines can actually become immunosuppressive. We showed that there is a species variation in the mechanisms of MSC-mediated immunosuppression： immunosuppression by cytokine-primed mouse MSCs is mediated by nitric oxide （NO）, whereas immunosuppression by cytokine-primed human MSCs is executed through indoleamine 2, 3-dioxygenase （IDO）. Additionally, upon stimulation with the inflammatory cytokines, both mouse and human MSCs secrete several leukocyte chemokines that apparently serve to attract immune cells into the proximity with MSCs, where NO or IDO is predicted to be most active. Therefore, immunosuppression by inflammatory cytokine-stimulated MSCs occurs via the concerted action of chemokines and immune-inhibitory NO or IDO produced by MSCs. Thus, our results provide novel information about the mechanisms of MSC-mediated immunosuppression and for better application of MSCs in treating tissue injuries induced by immune responses.
文摘We used a potent and specific monoclonal antibody to somatostatin to test the physiologic inhibitory role of the tetradecapeptide somatostatin on pancreatic secretion.Somatostatin immunoneutralization increased both the total amylase and volume of pancreatic secretion.Cholecystokinin-A receptor antagonism abolished the stimulatory effect of somatostatin immunoneutralization.We conclude that somatostatin tonically inhibits pancreatic secretion in fasted rats via inhibition of the release or action of cholecystokinin.Furthermore,the source of these peptides is likely islet delta cells and intrapancreatic neurons,respectively.
