Objective To induce islet grafting tolerance by intravenous injection of anti CD 4, anti CD 8 immunotoxins and donor soluble antigen Methods Fourteen days or 7 days prior to transplantation, the immunotoxin of...Objective To induce islet grafting tolerance by intravenous injection of anti CD 4, anti CD 8 immunotoxins and donor soluble antigen Methods Fourteen days or 7 days prior to transplantation, the immunotoxin of anti CD 4, anti CD 8 200?μg respectively, and donor soluble antigen 500?μg were intravenously injected and then 500 donor islets were transplanted under the left renal subcapsular space of diabetes recipients (Sprague Dawley rats) Results The islet grafting survival time for those recipients pretreated with immunotoxin and donor soluble antigen was >60 days ( P <0 01) The immunotoxins, donor soluble antigen treatment alone might only slightly prolong the grafting survival time Conclusion The anti CD 4, anti CD 8 immunotoxins jointly used with donor soluble antigen can induce donor specific immunotolerance展开更多
Objective: To determine the adjuvant potential of artemisinin with a soluble leishmanial antigen in vaccinating BALB/c mice. Methods: Seventy two female BALB/c mice were randomly assigned into six groups. The mice w...Objective: To determine the adjuvant potential of artemisinin with a soluble leishmanial antigen in vaccinating BALB/c mice. Methods: Seventy two female BALB/c mice were randomly assigned into six groups. The mice were vaccinated with soluble Leishmania antigens (SLA) alone, artemisinin co-administered with SLA, SLA and Bacille Calmette Gu fin (BCG) vaccine, and artemisinin and BCG alone. Unvaccinated mice formed the control group. The induction of cell-mediated immunity following vaccination was determined by measuring in vitro lymphocyte proliferation and the production of interleukin (IL)-4, IL-5 and gamma interferon (IFN-γ) determined by flow cytometry. Protection against L. major was determined by quantifying parasite burdens in L. major infected footpads using a limiting dilution assay and by measuring lesion sizes of the infected footpad compared to the contralateral uninfected footpad. Results: Mice receiving SLA plus artemisinin produced significantly high levels of IL-4 and IL-5 (P 〈 0.05) and low levels of IFN-γ, resulting in exacerbated disease. In addition, subcutaneous administration of SLA + artemisinin, artemisinin alone or SLA alone resulted in the development of large footpad swellings and high parasite loads that were comparable to those of the control unvaccinated mice (P 〉 0.05), resulting in exacerbated disease. Conclusion: These data suggest that artemisinin is not a suitable adjuvant for Leishmania vaccines. However, since artemisinin has been shown to be effective against Leishmania parasites in vitro and in vivo, further studies ought to be conducted to determine its immunochemotherapeutic potential when co-administered with Leishmania antigens.展开更多
Introduction: Human leukocyte antigen G (HLA-G) is a non-classical major histocompatibility complex (MHC) class Ib antigen characterized by a limited polymorphism. The expression of HLA-G at immune privileged sites an...Introduction: Human leukocyte antigen G (HLA-G) is a non-classical major histocompatibility complex (MHC) class Ib antigen characterized by a limited polymorphism. The expression of HLA-G at immune privileged sites and its ability to inhibit the effectors functions of immune cells has set HLA-G as a molecule of immune tolerance. This expression pattern is unique among HLA genes and suggests that HLA-G may be involved in interactions that are critical in establishing and/or maintaining pregnancy. Methods: Soluble HLA-G (sHLA-G) levels were measured using a BioVendor sHLA-G ELISA kit following the manufacturer’s protocol. The study participants include women undergoing spontaneous abortion, non-pregnant women, males and an archive sample of women who had normal vaginal deliveries without any complications and any history of malaria infection from gestation to delivery. Results: Soluble HLA-G levels were higher among women undergoing spontaneous abortion as compared to women who had normal vaginal delivery and non-pregnant women. Soluble HLA-G levels were also higher in second trimester as compared to first trimester in both women who had spontaneous abortions and women who had normal delivery. Conclusion: Although sHLA-G levels were higher among women undergoing spontaneous abortion as compared to non-pregnant women and women who had normal delivery, this may be playing a role in the maintenance of maternal immune tolerance to fetal antigen, since plasma sHLA-G levels increased with increasing trimester in both women who had normal delivery and women undergoing spontaneous abortion.展开更多
A 37oyear old woman presented with a 9oyear history of hepatitis of unknown origin and aminotransferases within a 3-fold upper limit of normal. Autoimmune hepatitis (AIH) was diagnosed on the basis of elevated amino...A 37oyear old woman presented with a 9oyear history of hepatitis of unknown origin and aminotransferases within a 3-fold upper limit of normal. Autoimmune hepatitis (AIH) was diagnosed on the basis of elevated aminotransferases, soluble liver antigen/liver pancreas (SLA/LP) autoantibodies and characteristic histology. Immunosuppressive therapy led to rapid normalization of aminotransferases. Two years later, the patient developed left sided hemisensory deficits under maintenance therapy of prednisolone and azathioprine (AZT). Later she developed right foot drop and paraesthesia in the ulnar innervation territory on both sides. Magnetic resonance imaging (MRI) and cerebral panangiography suggested cerebral vasculitis. Neurological investigation and electromyography disclosed multiplex neuritis (MN) probably due to vasculitis. Consistent with this diagnosis, autoantibodies to extractable nuclear antigens were detectable in serum. Immunosuppression was changed to oral 150 mg cyclophosphamide (CPMO) per day. Prednisolone was increased to 40 mg/d and then gradually tapered to 5 mg. Oral CPM was administered up to a total dose of 40 g and then substituted by 6 times of an intervall infusion therapy of CPM (600 mg/m^2). Almost complete motoric remission was achieved after 3 mo of CPM. Sensibility remained reduced in the right peroneal innervation territory. Follow-up of cranial MRI provided stable findings without any new or progressive lesions. This is the first report of multiplex neuritis in a patient with autoimmune hepatitis.展开更多
Available reports suggest that, Leishmania donovani antigen KMP-11 may be significant in the modulation of immune responses in visceral leishmaniasis (VL). This study evaluated vaccine prospect of presentation of KMP-...Available reports suggest that, Leishmania donovani antigen KMP-11 may be significant in the modulation of immune responses in visceral leishmaniasis (VL). This study evaluated vaccine prospect of presentation of KMP-11 antigen through murine dendritic cells against VL in infected BALB/c mice. We report here that immunization with KMP-11 delivered through bone marrow derived dendritic cells can lead to killing of L. donovani in infected BALB/c mice. Furthermore, the strategy to use KMP-11 as vaccine delivered through DCs can stimulate the production of IFN-g, IL-12, IL-2R and TNF-α with concomitant down-regulation of IL-10 and IL-4. Furthermore, anti-leishmanial defence function (ROS) of splenocytes was observed increased in the presence of DC-delivered KMP-11 vaccination accompanied with an increased p38-MAPK signalling in vaccinated splenocytes. We summarized from our data that KMP-11 delivered through DCs has potential for eliciting protective immunity through pro-inflammatory cytokines (IFN-γ, IL-12, IL-2, TNF-α) following an up-regulation in signalling event of p38-MAPK. Therefore the study suggests a new control strategy against VL in future.展开更多
文摘Objective To induce islet grafting tolerance by intravenous injection of anti CD 4, anti CD 8 immunotoxins and donor soluble antigen Methods Fourteen days or 7 days prior to transplantation, the immunotoxin of anti CD 4, anti CD 8 200?μg respectively, and donor soluble antigen 500?μg were intravenously injected and then 500 donor islets were transplanted under the left renal subcapsular space of diabetes recipients (Sprague Dawley rats) Results The islet grafting survival time for those recipients pretreated with immunotoxin and donor soluble antigen was >60 days ( P <0 01) The immunotoxins, donor soluble antigen treatment alone might only slightly prolong the grafting survival time Conclusion The anti CD 4, anti CD 8 immunotoxins jointly used with donor soluble antigen can induce donor specific immunotolerance
文摘Objective: To determine the adjuvant potential of artemisinin with a soluble leishmanial antigen in vaccinating BALB/c mice. Methods: Seventy two female BALB/c mice were randomly assigned into six groups. The mice were vaccinated with soluble Leishmania antigens (SLA) alone, artemisinin co-administered with SLA, SLA and Bacille Calmette Gu fin (BCG) vaccine, and artemisinin and BCG alone. Unvaccinated mice formed the control group. The induction of cell-mediated immunity following vaccination was determined by measuring in vitro lymphocyte proliferation and the production of interleukin (IL)-4, IL-5 and gamma interferon (IFN-γ) determined by flow cytometry. Protection against L. major was determined by quantifying parasite burdens in L. major infected footpads using a limiting dilution assay and by measuring lesion sizes of the infected footpad compared to the contralateral uninfected footpad. Results: Mice receiving SLA plus artemisinin produced significantly high levels of IL-4 and IL-5 (P 〈 0.05) and low levels of IFN-γ, resulting in exacerbated disease. In addition, subcutaneous administration of SLA + artemisinin, artemisinin alone or SLA alone resulted in the development of large footpad swellings and high parasite loads that were comparable to those of the control unvaccinated mice (P 〉 0.05), resulting in exacerbated disease. Conclusion: These data suggest that artemisinin is not a suitable adjuvant for Leishmania vaccines. However, since artemisinin has been shown to be effective against Leishmania parasites in vitro and in vivo, further studies ought to be conducted to determine its immunochemotherapeutic potential when co-administered with Leishmania antigens.
文摘Introduction: Human leukocyte antigen G (HLA-G) is a non-classical major histocompatibility complex (MHC) class Ib antigen characterized by a limited polymorphism. The expression of HLA-G at immune privileged sites and its ability to inhibit the effectors functions of immune cells has set HLA-G as a molecule of immune tolerance. This expression pattern is unique among HLA genes and suggests that HLA-G may be involved in interactions that are critical in establishing and/or maintaining pregnancy. Methods: Soluble HLA-G (sHLA-G) levels were measured using a BioVendor sHLA-G ELISA kit following the manufacturer’s protocol. The study participants include women undergoing spontaneous abortion, non-pregnant women, males and an archive sample of women who had normal vaginal deliveries without any complications and any history of malaria infection from gestation to delivery. Results: Soluble HLA-G levels were higher among women undergoing spontaneous abortion as compared to women who had normal vaginal delivery and non-pregnant women. Soluble HLA-G levels were also higher in second trimester as compared to first trimester in both women who had spontaneous abortions and women who had normal delivery. Conclusion: Although sHLA-G levels were higher among women undergoing spontaneous abortion as compared to non-pregnant women and women who had normal delivery, this may be playing a role in the maintenance of maternal immune tolerance to fetal antigen, since plasma sHLA-G levels increased with increasing trimester in both women who had normal delivery and women undergoing spontaneous abortion.
基金Supported by the Deutsche Forschungsgemeinschaft (SFB 548)
文摘A 37oyear old woman presented with a 9oyear history of hepatitis of unknown origin and aminotransferases within a 3-fold upper limit of normal. Autoimmune hepatitis (AIH) was diagnosed on the basis of elevated aminotransferases, soluble liver antigen/liver pancreas (SLA/LP) autoantibodies and characteristic histology. Immunosuppressive therapy led to rapid normalization of aminotransferases. Two years later, the patient developed left sided hemisensory deficits under maintenance therapy of prednisolone and azathioprine (AZT). Later she developed right foot drop and paraesthesia in the ulnar innervation territory on both sides. Magnetic resonance imaging (MRI) and cerebral panangiography suggested cerebral vasculitis. Neurological investigation and electromyography disclosed multiplex neuritis (MN) probably due to vasculitis. Consistent with this diagnosis, autoantibodies to extractable nuclear antigens were detectable in serum. Immunosuppression was changed to oral 150 mg cyclophosphamide (CPMO) per day. Prednisolone was increased to 40 mg/d and then gradually tapered to 5 mg. Oral CPM was administered up to a total dose of 40 g and then substituted by 6 times of an intervall infusion therapy of CPM (600 mg/m^2). Almost complete motoric remission was achieved after 3 mo of CPM. Sensibility remained reduced in the right peroneal innervation territory. Follow-up of cranial MRI provided stable findings without any new or progressive lesions. This is the first report of multiplex neuritis in a patient with autoimmune hepatitis.
文摘Available reports suggest that, Leishmania donovani antigen KMP-11 may be significant in the modulation of immune responses in visceral leishmaniasis (VL). This study evaluated vaccine prospect of presentation of KMP-11 antigen through murine dendritic cells against VL in infected BALB/c mice. We report here that immunization with KMP-11 delivered through bone marrow derived dendritic cells can lead to killing of L. donovani in infected BALB/c mice. Furthermore, the strategy to use KMP-11 as vaccine delivered through DCs can stimulate the production of IFN-g, IL-12, IL-2R and TNF-α with concomitant down-regulation of IL-10 and IL-4. Furthermore, anti-leishmanial defence function (ROS) of splenocytes was observed increased in the presence of DC-delivered KMP-11 vaccination accompanied with an increased p38-MAPK signalling in vaccinated splenocytes. We summarized from our data that KMP-11 delivered through DCs has potential for eliciting protective immunity through pro-inflammatory cytokines (IFN-γ, IL-12, IL-2, TNF-α) following an up-regulation in signalling event of p38-MAPK. Therefore the study suggests a new control strategy against VL in future.