CD4＋CD25＋ regulatory T cells （Tregs） play an important role in maintaining host immune tolerance via regulation of the phenotype and function of the innate and adaptive immune cells. Whether allogeneic CD4＋CD25＋...CD4＋CD25＋ regulatory T cells （Tregs） play an important role in maintaining host immune tolerance via regulation of the phenotype and function of the innate and adaptive immune cells. Whether allogeneic CD4＋CD25＋ Tregs can regulate recipient mouse macrophages is unknown. The effect of allogeneic donor CD4＋CD25＋ Tregs on recipient mouse resident F4/80＋macrophages was investigated using a mouse model in which allogeneic donor CD4＋CD25＋ Tregs were adoptively transferred into the peritoneal cavity of host NOD-scid mice. The phenotype and function of the recipient macrophages were then assayed. The peritoneal F4/80＋ macrophages in the recipient mice that received the allogeneic CD4＋CD25＋ Tregs expressed significantly higher levels of CD23 and programmed cell death-ligand I（PD-L1） and lower levels of CD80, CD86, CD40 and MHC II molecules compared to the mice that received either allogeneic CD4＋CD25- T cells （Teffs） or no cells. The resident F4/80＋ macrophages of the recipient mice injected with the allogeneic donor CD4＋CD25＋ Tregs displayed significantly increased phagocytosis of chicken red blood cells （cRBCs） and arginase activity together with increased IL-IO production, whereas these macrophages also showed decreased immunogenicity and nitric oxide （NO） production. Blocking arginase partially but significantly reversed the effects of CD4＋CD25＋ Tregs with regard to the induction of the M2 macrophages in vivo. Therefore, the allogeneic donor CD4＋CD25＋ Tregs can induce the M2 macrophages in recipient mice at least in part via an arginase pathway. We have provided in vivo evidence to support the unknown pathways by which allogeneic donor CD4＋CD25＋ Tregs regulate innate immunity in recipient mice by promoting the differentiation of M2 macrophages.展开更多
New nucleos(t)ide analogues(NAs) with high genetic barrier to hepatitis B virus(HBV) resistance(such as entecavir, tenofovir) have improved the prognosis of patients with HBV decompensated cirrhosis and have prevented...New nucleos(t)ide analogues(NAs) with high genetic barrier to hepatitis B virus(HBV) resistance(such as entecavir, tenofovir) have improved the prognosis of patients with HBV decompensated cirrhosis and have prevented HBV recurrence after liver transplantation(LT). NAs are considered the most proper approach for HBV infection in patients under renal replacement therapy but their doses should be adjusted according to the patient's creatinine clearance. In addition, physi-cians should be aware of the potential nephrotoxicity. However, patients with chronic hepatitis C and decom-pensated cirrhosis can receive only one therapeutic option before LT, as well as for Hepatitis C virus(HCV) recurrence after LT, which is the combination of sub-cutaneous Peg-IFN and ribavirin. Generally, therapy for HCV after renal transplantation should be avoided. Although the optimal antiviral therapy for HCV infec-tion has not been established, attention has turned to a new, oral direct acting antiviral treatment which marks a promising strategy in prognosis and in amelioration of these diseases.展开更多
Islet transplantation is characterized by the transplantation of isolated islets from donor pancreata into a diabetic recipient. Although it is a viable choice in the treatment of insulin dependent diabetes mellitus, ...Islet transplantation is characterized by the transplantation of isolated islets from donor pancreata into a diabetic recipient. Although it is a viable choice in the treatment of insulin dependent diabetes mellitus, most patients (approximately 90%) require insulin five years after transplantation. Recently, the co-transplantation of mesenchymal stem cells (MSCs) and islets in animal studies has revealed the effectiveness of MSCs co-transplantation for improving islet function. Themechanisms underlying the beneficial impact of MSCs include immunomodulation and the promotion of angiogenesis. In this review, we discuss MSCs and how they support improved graft survival and function.展开更多
Hepatocellular carcinoma(HCC) is an aggressive tumor that often occurs in the setting of chronic liver disease.Many patients do not initially manifest any symptoms of HCC and present late when cure with surgical resec...Hepatocellular carcinoma(HCC) is an aggressive tumor that often occurs in the setting of chronic liver disease.Many patients do not initially manifest any symptoms of HCC and present late when cure with surgical resection or transplantation is no longer possible.For this reason,patients at high risk for developing HCC are subjected to frequent screening processes.The surgical management of HCC is complex and requires an inter-disciplinary approach.Hepatic resection is the treatment of choice for HCC in patients without cirrhosis and is indicated in some patients with early cirrhosis(Child-Pugh A).Liver transplantation has emerged in the past decade as the standard of care for patients with cirrhosis and HCC meeting Milan criteria and in select patients with HCC beyond Milan criteria.Loco-regional therapy with transarterial chemoembolization,transarterial embolization,radiofrequency ablation and other similar local treatments can be used as neo-adjuvant therapy to downstage HCC to within Milan criteria or as a bridge to transplantation in patients on transplant wait list.展开更多
We describe the effects of Darbepoietin-alfa (Darbe) administration in Multiple Myeloma (MM) after autologous he-mopoietic progenitor cell transplantation (AHPCT). 26 MM patients undergoing AHPCT entered this study. 3...We describe the effects of Darbepoietin-alfa (Darbe) administration in Multiple Myeloma (MM) after autologous he-mopoietic progenitor cell transplantation (AHPCT). 26 MM patients undergoing AHPCT entered this study. 34 hemo-globin (Hb)-matched patients who had not received recombinant human erythropoietin (Epo) or Darbe and were treated with the same protocol were retrospectively selected for comparative data. Darbe (150 micro g total dose/weekly) was initiating in four weeks after AHPCT, with the aim of achieving an Hb level of ≥11 g/dl. The time to response to Darbe therapy was longer in the patients with Hb < 10 g/dL (p = 0.05) and with endogenous Epo levels ≤ 50 mU/ml (p = 0.0098). Hb level on day 60 and 90 after AHPCT, was faster for Darbe recipients (12.5, range 9.4 - 15.4, vs 10.6, range 8.8 - 13.4 g/dL, p = 0.0001, and 13.5, range 12.3 - 14.3, vs 12, range 9.8 - 14 g/dL, respectively, p = 0.0001). The need for Red Blood Cells transfusion, included in the period of 30 - 90 days post- AHPCT was similar (p = ns). This study demonstrates the accelerating effect of Darbe on Hb increase in the setting evaluated and shows that this effect signify- cantly depends on the endogenous Epo level at the start of treatment. The strategy of giving Darbe around 1 month after high-dose melphalan (HDM) doesn’t reduce RBC transfusion requirement.展开更多
The outbreak of coronavirus disease 2019 (COVID-19) has resulted in significant morbidity and mortality worldwide. Vaccination against coronavirus disease 2019 is a use-ful weapon to combat the virus. Patients with ch...The outbreak of coronavirus disease 2019 (COVID-19) has resulted in significant morbidity and mortality worldwide. Vaccination against coronavirus disease 2019 is a use-ful weapon to combat the virus. Patients with chronic liver diseases (CLDs), including compensated or decompensated liver cirrhosis and noncirrhotic diseases, have a decreased immunologic response to coronavirus disease 2019 vaccines. At the same time, they have increased mortality if infected. Current data show a reduction in mortality when patients with chronic liver diseases are vaccinated. A suboptimal vac-cine response has been observed in liver transplant recipi-ents, especially those receiving immunosuppressive therapy, so an early booster dose is recommended to achieve a better protective effect. Currently, there are no clinical data com-paring the protective efficacy of different vaccines in patients with chronic liver diseases. Patient preference, availability of the vaccine in the country or area, and adverse effect profiles are factors to consider when choosing a vaccine. There have been reports of immune-mediated hepatitis after coronavi-rus disease 2019 vaccination, and clinicians should be aware of that potential side effect. Most patients who developed hepatitis after vaccination responded well to treatment with prednisolone, but an alternative type of vaccine should be considered for subsequent booster doses. Further prospec-tive studies are required to investigate the duration of immu-nity and protection against different viral variants in patients with chronic liver diseases or liver transplant recipients, as well as the effect of heterologous vaccination.展开更多
Hepatitis C virus(HCV) almost recurs after liver transplantation for HCV-related liver cirrhosis or hepatocellular carcinoma. Management of HCV recurrence after liver transplantation is challenging because the traditi...Hepatitis C virus(HCV) almost recurs after liver transplantation for HCV-related liver cirrhosis or hepatocellular carcinoma. Management of HCV recurrence after liver transplantation is challenging because the traditional interferon-based therapy is often patient-intolerable and inducing cytopenia, and dose reduction is needed. The response rate in liver recipients is inferior to those of chronic HCV infection. About 5 percent of liver recipients receiving interferon-based therapy would develop immune-mediated graft injury and may need retransplantation. Recent advances of anti-HCV therapy for chronic HCV infection has evolutionary changing the schema from interferon-based, to interferon-free, and even to ribavirin-free, all oral combinations for pan-genotypes. Management of HCV recurrence after liver transplantation is currently evolving too and promising results will soon come to the stage. This "fast-track" concise review focuses on the issues relevant to HCV recurrence after liver transplantation and provides up-to-date information of the trend of the management. A real-world case demonstration of management was presented here to illustrate the potential complications of anti-HCV therapy after liver transplantation.展开更多
基金The authors wish to thank Drs Shuping Zhou and Zeqing Niu for their kind review of the manuscript, Ms ling Wang, Mr Yabing Liu and Ms Xiaoqiu Liu for their expert technical assistance, Ms Qinghuan Li and ]ianxia Peng for their excellent laboratory management and Mr Baisheng Ren for his outstanding animal husbandry. This work was supported by grants from the National Natural Science Foundation （C81072396, U0832003, YZ C31171407 and 81273201, GL）, the Ministry of Science and Technology of China （2010CB945301, YZ） and the Chinese Academy of Sciences for Distinguished Young Scientists （KSCX2-EW-Q-7, GL）.
文摘CD4＋CD25＋ regulatory T cells （Tregs） play an important role in maintaining host immune tolerance via regulation of the phenotype and function of the innate and adaptive immune cells. Whether allogeneic CD4＋CD25＋ Tregs can regulate recipient mouse macrophages is unknown. The effect of allogeneic donor CD4＋CD25＋ Tregs on recipient mouse resident F4/80＋macrophages was investigated using a mouse model in which allogeneic donor CD4＋CD25＋ Tregs were adoptively transferred into the peritoneal cavity of host NOD-scid mice. The phenotype and function of the recipient macrophages were then assayed. The peritoneal F4/80＋ macrophages in the recipient mice that received the allogeneic CD4＋CD25＋ Tregs expressed significantly higher levels of CD23 and programmed cell death-ligand I（PD-L1） and lower levels of CD80, CD86, CD40 and MHC II molecules compared to the mice that received either allogeneic CD4＋CD25- T cells （Teffs） or no cells. The resident F4/80＋ macrophages of the recipient mice injected with the allogeneic donor CD4＋CD25＋ Tregs displayed significantly increased phagocytosis of chicken red blood cells （cRBCs） and arginase activity together with increased IL-IO production, whereas these macrophages also showed decreased immunogenicity and nitric oxide （NO） production. Blocking arginase partially but significantly reversed the effects of CD4＋CD25＋ Tregs with regard to the induction of the M2 macrophages in vivo. Therefore, the allogeneic donor CD4＋CD25＋ Tregs can induce the M2 macrophages in recipient mice at least in part via an arginase pathway. We have provided in vivo evidence to support the unknown pathways by which allogeneic donor CD4＋CD25＋ Tregs regulate innate immunity in recipient mice by promoting the differentiation of M2 macrophages.
文摘New nucleos(t)ide analogues(NAs) with high genetic barrier to hepatitis B virus(HBV) resistance(such as entecavir, tenofovir) have improved the prognosis of patients with HBV decompensated cirrhosis and have prevented HBV recurrence after liver transplantation(LT). NAs are considered the most proper approach for HBV infection in patients under renal replacement therapy but their doses should be adjusted according to the patient's creatinine clearance. In addition, physi-cians should be aware of the potential nephrotoxicity. However, patients with chronic hepatitis C and decom-pensated cirrhosis can receive only one therapeutic option before LT, as well as for Hepatitis C virus(HCV) recurrence after LT, which is the combination of sub-cutaneous Peg-IFN and ribavirin. Generally, therapy for HCV after renal transplantation should be avoided. Although the optimal antiviral therapy for HCV infec-tion has not been established, attention has turned to a new, oral direct acting antiviral treatment which marks a promising strategy in prognosis and in amelioration of these diseases.
基金Supported by Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan, C: 22591513the Uehara Memorial Foundation, NSGrant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan, B: 22390253, SE
文摘Islet transplantation is characterized by the transplantation of isolated islets from donor pancreata into a diabetic recipient. Although it is a viable choice in the treatment of insulin dependent diabetes mellitus, most patients (approximately 90%) require insulin five years after transplantation. Recently, the co-transplantation of mesenchymal stem cells (MSCs) and islets in animal studies has revealed the effectiveness of MSCs co-transplantation for improving islet function. Themechanisms underlying the beneficial impact of MSCs include immunomodulation and the promotion of angiogenesis. In this review, we discuss MSCs and how they support improved graft survival and function.
文摘Hepatocellular carcinoma(HCC) is an aggressive tumor that often occurs in the setting of chronic liver disease.Many patients do not initially manifest any symptoms of HCC and present late when cure with surgical resection or transplantation is no longer possible.For this reason,patients at high risk for developing HCC are subjected to frequent screening processes.The surgical management of HCC is complex and requires an inter-disciplinary approach.Hepatic resection is the treatment of choice for HCC in patients without cirrhosis and is indicated in some patients with early cirrhosis(Child-Pugh A).Liver transplantation has emerged in the past decade as the standard of care for patients with cirrhosis and HCC meeting Milan criteria and in select patients with HCC beyond Milan criteria.Loco-regional therapy with transarterial chemoembolization,transarterial embolization,radiofrequency ablation and other similar local treatments can be used as neo-adjuvant therapy to downstage HCC to within Milan criteria or as a bridge to transplantation in patients on transplant wait list.
文摘We describe the effects of Darbepoietin-alfa (Darbe) administration in Multiple Myeloma (MM) after autologous he-mopoietic progenitor cell transplantation (AHPCT). 26 MM patients undergoing AHPCT entered this study. 34 hemo-globin (Hb)-matched patients who had not received recombinant human erythropoietin (Epo) or Darbe and were treated with the same protocol were retrospectively selected for comparative data. Darbe (150 micro g total dose/weekly) was initiating in four weeks after AHPCT, with the aim of achieving an Hb level of ≥11 g/dl. The time to response to Darbe therapy was longer in the patients with Hb < 10 g/dL (p = 0.05) and with endogenous Epo levels ≤ 50 mU/ml (p = 0.0098). Hb level on day 60 and 90 after AHPCT, was faster for Darbe recipients (12.5, range 9.4 - 15.4, vs 10.6, range 8.8 - 13.4 g/dL, p = 0.0001, and 13.5, range 12.3 - 14.3, vs 12, range 9.8 - 14 g/dL, respectively, p = 0.0001). The need for Red Blood Cells transfusion, included in the period of 30 - 90 days post- AHPCT was similar (p = ns). This study demonstrates the accelerating effect of Darbe on Hb increase in the setting evaluated and shows that this effect signify- cantly depends on the endogenous Epo level at the start of treatment. The strategy of giving Darbe around 1 month after high-dose melphalan (HDM) doesn’t reduce RBC transfusion requirement.
文摘The outbreak of coronavirus disease 2019 (COVID-19) has resulted in significant morbidity and mortality worldwide. Vaccination against coronavirus disease 2019 is a use-ful weapon to combat the virus. Patients with chronic liver diseases (CLDs), including compensated or decompensated liver cirrhosis and noncirrhotic diseases, have a decreased immunologic response to coronavirus disease 2019 vaccines. At the same time, they have increased mortality if infected. Current data show a reduction in mortality when patients with chronic liver diseases are vaccinated. A suboptimal vac-cine response has been observed in liver transplant recipi-ents, especially those receiving immunosuppressive therapy, so an early booster dose is recommended to achieve a better protective effect. Currently, there are no clinical data com-paring the protective efficacy of different vaccines in patients with chronic liver diseases. Patient preference, availability of the vaccine in the country or area, and adverse effect profiles are factors to consider when choosing a vaccine. There have been reports of immune-mediated hepatitis after coronavi-rus disease 2019 vaccination, and clinicians should be aware of that potential side effect. Most patients who developed hepatitis after vaccination responded well to treatment with prednisolone, but an alternative type of vaccine should be considered for subsequent booster doses. Further prospec-tive studies are required to investigate the duration of immu-nity and protection against different viral variants in patients with chronic liver diseases or liver transplant recipients, as well as the effect of heterologous vaccination.
文摘Hepatitis C virus(HCV) almost recurs after liver transplantation for HCV-related liver cirrhosis or hepatocellular carcinoma. Management of HCV recurrence after liver transplantation is challenging because the traditional interferon-based therapy is often patient-intolerable and inducing cytopenia, and dose reduction is needed. The response rate in liver recipients is inferior to those of chronic HCV infection. About 5 percent of liver recipients receiving interferon-based therapy would develop immune-mediated graft injury and may need retransplantation. Recent advances of anti-HCV therapy for chronic HCV infection has evolutionary changing the schema from interferon-based, to interferon-free, and even to ribavirin-free, all oral combinations for pan-genotypes. Management of HCV recurrence after liver transplantation is currently evolving too and promising results will soon come to the stage. This "fast-track" concise review focuses on the issues relevant to HCV recurrence after liver transplantation and provides up-to-date information of the trend of the management. A real-world case demonstration of management was presented here to illustrate the potential complications of anti-HCV therapy after liver transplantation.
