Background Recent recognition is that Th2 response is insufficient to fully explain the aetiology of asthma. Other CD4^＋ T cells subsets might play a role in asthma. We investigated the relative abundance and activit...Background Recent recognition is that Th2 response is insufficient to fully explain the aetiology of asthma. Other CD4^＋ T cells subsets might play a role in asthma. We investigated the relative abundance and activities of Thl, Th2, Th17 and CD4^＋CD25^＋ Treg cells in patients with allergic asthma. Methods Twenty-two patients with mild asthma, 17 patients with moderate to severe asthma and 20 healthy donors were enrolled. All patients were allergic to house dust mites. Plasma total IgE, pulmonary function and Asthma Control Questionnaire were assessed. The proportions of peripheral blood Thl, Th2, Th17 and CD4^＋CD25^＋ Treg cells were determined by flow cytometry. The expression of cytokines in plasma and Jn the culture supernatant of peripheral blood mononuclear cells was determined by enzyme linked, immunosorbent assay. Results The frequency of blood Th2 cells and IL-4 levels in plasma and culture supernatant of peripheral blood mononuclear cells were increased in all patients with allergic asthma. The frequency of Th17 cells and the plasma and culture supernatant levels of IL-17 were increased, whereas the frequency of CD4^＋CD25^＋ Treg cells and plasma IL-10 levels were decreased in patients with moderate to severe asthma. Dermatophagoides pteronyssinus specific IgE levels were positively correlated with the percentage of blood Th2 cells and plasma IL-4 levels. Forced expiratory volume in the first second was negatively correlated with the frequency of Th17 cells and plasma IL-17 levels, and positively correlated with the frequency of Treg cells. However, mean Asthma Control Questionnaire scores were positively correlated with the frequency of Th17 cells and plasma IL-17 levels, and negatively correlated with the frequency of Treg cells. Conclusions Imbalances in Thl/Th2 and Th17/Treg were found in patients with allergic asthma. Furthermore, elevated Th17 cell responses, the absence of Tregs and an imbalance in Th17/Treg levels were associated with moderate to severe asthma.展开更多
Hepatitis B virus(HBV) infection is one the leading risk factors for chronic hepatitis, liver fibrosis, cirrhosis and hepatocellular cancer(HCC), which are a major global health problem. A large number of clinical stu...Hepatitis B virus(HBV) infection is one the leading risk factors for chronic hepatitis, liver fibrosis, cirrhosis and hepatocellular cancer(HCC), which are a major global health problem. A large number of clinical studies have shown that chronic HBV persistent infection causes the dysfunction of innate and adaptive immune response involving monocytes/macrophages, dendritic cells, natural killer(NK) cells, T cells. Among these immune cells, cell subsets with suppressive features have been recognized such as myeloid derived suppressive cells(MDSC),NK-reg, T-reg, which represent a critical regulatory system during liver fibrogenesis or tumourigenesis. However, the mechanisms that link HBVinduced immune dysfunction and HBV-related liver diseases are not understood.In this review we summarize the recent studies on innate and adaptive immune cell dysfunction in chronic HBV infection, liver fibrosis, cirrhosis, and HCC, and further discuss the potential mechanism of HBV-induced immunosuppressive cascade in HBV infection and consequences. It is hoped that this article will help ongoing research about the pathogenesis of HBV-related hepatic fibrosis and HBV-related HCC.展开更多
Background Astragalus polysaccharides （APS）, the main active extract from Astragalus membranaceus （a traditional Chinese medicinal herb）, is associated with a variety of immunomodulatory activities. The purpose of...Background Astragalus polysaccharides （APS）, the main active extract from Astragalus membranaceus （a traditional Chinese medicinal herb）, is associated with a variety of immunomodulatory activities. The purpose of the present study was to examine the effect of APS on the function of Treg cells in the tumor microenvironment of human hepatocellular carcinoma （HCC） and to identify the pharmacologic mechanism of APS responsible for the anti-chemotactic activity in CD4＋CD25^highTreq cells in tumor site of HCC.展开更多
Hepatocellular carcinoma (HCC) is one of the most com- mon cancers in the world with an annual incidence of more than 500 000 in the year 2000. Its incidence is rising in many countries. Recently, it has been estimate...Hepatocellular carcinoma (HCC) is one of the most com- mon cancers in the world with an annual incidence of more than 500 000 in the year 2000. Its incidence is rising in many countries. Recently, it has been estimated that about 53% of HCC cases in the world are related to hepatitis B virus (HBV). The epidemiological association of HBV with HCC is well established. In recent studies, it was revealed that HBsAg carriers have a 25-37 times increased risk of developing HCC as compared to non-infected people. At present, HBV-associated carcinogenesis can be seen as a multi-factorial process that includes both direct and indirect mechanisms that might act synergistically. The integration of HBV DNA into the host genome occurs at early steps of clonal tumor expansion. The integration has been shown in a number of cases to affect a variety of cancer- related genes and to exert insertional mutagenesis. The permanent liver inflammation, induced by the immune response, resulting in a degeneration and regeneration process confers to the accumulation of critical mutations in the host genome. In addition to this, the regulatory proteins HBx and the PreS2 activators that can be encoded by the integrate exert a tumor promoter-like function resulting in positive selection of cells producing a functional regulatory protein. Gene expression profiling and proteomic techniques may help to characterize the molecular mechanisms driving HBV-associated carcino- genesis, and thus potentially identify new strategies in diagnosis and therapy.展开更多
Background and objective： Umbilical cord （UC）-derived mesenchymal stem cells （MSCs） have shown immunoregulation of various immune cells. The aim of this study was to investigate the mechanism of UC MSCs in the re...Background and objective： Umbilical cord （UC）-derived mesenchymal stem cells （MSCs） have shown immunoregulation of various immune cells. The aim of this study was to investigate the mechanism of UC MSCs in the regulation of peripheral regulatory T cells （Treg） and T helper 17 （Th17） cells in patients with systemic lupus erythematosus （SLE）. Methods： Thirty patients with active SLE, refractory to conventional therapies, were given UC MSCs infusions. The percentages of peripheral blood CD4＋CD25＋Foxp3＋ regulatory T cells （Treg） and CD3＋CD8-1L17A＋ Th17 cells and the mean fluorescence intensities （MFI） of Foxp3 and IL- 17 were measured at I week, I month, 3 months, 6 months, and 12 months after MSCs transplantation （MSCT）. Serum cytokines, including transforming growth factor beta （TGF-β）, tumor necrosis factor alpha （TNF-α）, interleukin 6 （IL-6）, and IL-17A were detected using ELISA. Peripheral blood mononuclear cells from patients were collected and co-cultured with UC MSCs at ratios of 1：1, 10：1, and 50：1, respectively, for 72 h to detect the proportions of Treg and Th17 cells and the MFIs of Foxp3 and IL-17 were determined by flow cytometry. The cytokines in the supernatant solution were detected using ELISA. Inhibitors targeting TGF-β, IL-6, indoleamine 2,3-dioxygenase （IDO）, and prostaglandin E2 were added to the co-culture system, and the percentages of Treg and Th17 cells were observed. Results： The percentage of peripheral Treg and Foxp3 MFI increased 1 week, 1 month, and 3 months after UC MSCs transplantation, while the Th17 proportion and MFI of IL-17 decreased 3 months, 6 months, and 12 months after the treatment, along with an increase in serum TGF-β at I week, 3 months, and 12 months and a decrease in serum TNF-a beginning at I week. There were no alterations in serums IL-6 and IL-17A before or after MSCT. In vitro studies showed that the UC MSCs dose-dependently up-regulated peripheral Treg proportion in SLE patients, which was no展开更多
The balance between immune effector cells and immunosuppressive cells and how this regulates the tumor microenvironment has been well described.A significant contribution of immune regulatory cells,including regulator...The balance between immune effector cells and immunosuppressive cells and how this regulates the tumor microenvironment has been well described.A significant contribution of immune regulatory cells,including regulatory T cells,to tumor progression has been widely reported.An emerging body of evidence has recently recognized a role for B cells in modulating the immune response to tumors and lymphoid malignancies.Regulatory B cells(Bregs)are a newly designated subset of B cells that have been shown to play a pivotal role in regulating immune responses involved in inflammation,autoimmunity and,more recently,cancer.Bregs can suppress diverse cell subtypes,including T cells,through the secretion of anti-inflammatory mediators,such as IL-10,and can facilitate the conversion of T cells to regulatory T cells,thus attenuating anti-tumor immune responses.Similar B-cell subpopulations have been reported to be recruited to the tumor but to acquire their immunosuppressive properties within the tumor bed and thereby attenuate anti-tumor immune responses.However,despite a pivotal role for Bregs in promoting inflammation and carcinogenesis,the phenotypic diversity of the cell surface markers that are unique to Bregs remains unclear in mice and humans.In this review,we summarize the characteristics of Bregs and review our current knowledge of Bregs and their inhibition of anti-tumor immune responses in murine tumor models and cancer patients.展开更多
The homeostasis of the immune system depends on the balance between the immune response to an invaded pathogen and the immune tolerance to self antigens. Both central and peripheral tolerances are important mechanisms...The homeostasis of the immune system depends on the balance between the immune response to an invaded pathogen and the immune tolerance to self antigens. Both central and peripheral tolerances are important mechanisms for the induction and maintenance of T cell tolerance. Recently, much attention has been paid to regulatory T cells （Treg）, which play a significant role in maintaining peripheral immune tolerance. So far, there has been no satisfactory advance regarding the surface markers of Treg cells, as none is unique for Treg cells. In this review, we summarize some important molecules expressed in naturally occurring CD4^＋CD25^＋ Treg cells （nTreg）, including forkhead/winged-helix family transcriptional repressor p3 （Foxp3）, the tumor necrosis factor receptor （TNFR） family, CD28/CTLA4 molecules, chemokine receptors, Toll-like receptors （TLRs）, membrane- bound TGF-β and other molecules, such as neuropilin-1, lymphocyte activation gene-3 （LAG）-3 and granzyme. This review provides a collective view on current studies of nTreg cell activation and development related to the expression of molecules and cell phenotype markers, which is important for elucidation of nTreg cell origin, development and function. Cellular ＆ Molecular Immunology. 2006;3（3）：189-195.展开更多
Cross-talk has been shown to occur between the immune system and bone metabolism pathways.In the present study,we investigated the impact of CD4^(+)CD25^(+)Foxp3^(+) regulatory T(Treg)cells on osteoclastogenesis and b...Cross-talk has been shown to occur between the immune system and bone metabolism pathways.In the present study,we investigated the impact of CD4^(+)CD25^(+)Foxp3^(+) regulatory T(Treg)cells on osteoclastogenesis and bone resorption.Treg cells that were isolated and purified from peripheral blood mononuclear cells(PBMCs)of healthy adults inhibited both the differentiation of osteoclasts(OCs)from human embryo bone marrow cells(BMCs)and the pit formation in a dose-dependent manner.In cell cocultures,the production levels of both interleukin-10(IL-10)and transforming growth factor-beta 1(TGF-β1)were proportionally upregulated as the ratio of Treg cells to BMCs was increased,and the inhibition of OC differentiation and bone resorption by Treg cells was completely reversed by anti-IL-10 and anti-TGF-β1 antibodies.Treatment of BMC and Treg cell cocultures with 17β-estradiol(E2)at concentrations between 10^(-7) and 10^(-9) mol/l suppressed OC differentiation and bone resorption more efficiently than it did in cultures of BMCs alone;this enhanced suppression occurred via the stimulation of Treg cell IL-10 and TGF-b1 expression.These data suggest that Treg cells suppress OC differentiation and bone resorption by secreting IL-10 and TGF-β1.E2 enhances the suppressive effects of Treg cells on OC differentiation and bone resorption by stimulating IL-10 and TGF-β1 secretion from these cells.Therefore,Treg cell-derived IL-10 and TGF-b1 are likely involved in the regulation of E2 on bone metabolism and represent potential therapeutic targets for the treatment of postmenopausal osteoporosis(PMO).展开更多
AIM: To investigate the role of T helper 17 cells (Th17) and regulatory T cells (Treg) in hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF).METHODS: We enrolled 79 patients with HBV infection into ...AIM: To investigate the role of T helper 17 cells (Th17) and regulatory T cells (Treg) in hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF).METHODS: We enrolled 79 patients with HBV infection into the study, 50 patients with HBV-related ACLF and 29 patients with chronic hepatitis B (CHB), from the First Affiliated Hospital of Medical College from January 2009 to June 2012. The ACLF patients were diagnosed according to the criteria recommended by The 19th Conference of the Asian Pacific Association for the Study of the Liver in 2009. Twenty healthy individuals with a similar gender and age structures to the two patient groups were also included as the normal controls (NC). Of the 50 ACLF patients, 28 were subsequently classified as non-survivors: 19 patients died from multiorgan failure, 3 underwent liver transplantation, and 6 discontinued therapy during follow-up because of financial reasons. The remaining 22 ACLF patients whose liver and anticoagulation function recovered to nearly normal levels within the next 6 mo were classified as survivors. The number of circulating Treg and Th17 cells was determined upon diagnosis and during the 8th week of follow-up through flow cytometry. RESULTS: The percentage of circulating Treg cells in the ACLF group was significantly higher than that in the CHB group (5.50% ± 1.15% vs 3.30% ± 1.13%, P < 0.01). The percentages of circulating Th17 cells in the ACLF and the CHB groups were significantly higher than that in the NC group (6.32% ± 2.22% vs 1.56% ± 0.44%, P < 0.01; 3.53% ± 1.65% vs 1.56% ± 0.44%, P < 0.01). No significant difference in Treg cell to Th17 cell ratio was observed between the ACLF group and the CHB group (0.98 ± 0.44 vs 1.12 ± 0.64, P = 0.991), whereas those in the two HBV infection groups were significantly lower than that in the NC group (1.85 ± 1.22; both P < 0.01). The percentage of Treg cells in the survivors during the 8th week of follow-up was significantly lower than that during peak ACLF severity [total bilirubin (TBIL) 展开更多
B cells are generally considered to be positive regulators of the immune response because of their capability to produce antibodies, including autoantibodies. The production of antibodies facilitates optimal CD4＋ T-c...B cells are generally considered to be positive regulators of the immune response because of their capability to produce antibodies, including autoantibodies. The production of antibodies facilitates optimal CD4＋ T-cell activation because B cells serve as antigen-presenting cells and exert other modulatory functions in immune responses. However, certain B cells can also negatively regulate the immune response by producing regulatory cytokines and directly interacting with pathogenic T cells via cell-to-cell contact. These types of B Cells are defined as regulatory B （Breg） cells. The regulatory function of Breg cells has been demonstrated in mouse models of inflammation, cancer, transplantation, and particularly in autoimmunity. In this review, we focus on the recent advances that lead to the understanding of the development and function of Breg cells and the implications of B cells in human autoimmune diseases.展开更多
AIM: Persistent hepatitis B virus (HBV) infection is characterized by a weak CD8+ T cell response to HBV. Immunotherapeutic strategies that overcome tolerance and boost these suboptimal responses may facilitate viral ...AIM: Persistent hepatitis B virus (HBV) infection is characterized by a weak CD8+ T cell response to HBV. Immunotherapeutic strategies that overcome tolerance and boost these suboptimal responses may facilitate viral clearance in chronically infected individuals. Therefore, we examined whether CD25+CD4+ regulatory T (Treg) cells might be involved in a inhibition of CD8+T cell priming or in the modulation of the magnitude of the 'peak' antiviral CD8+ T cell response primed by DNA immunization. METHODS: B10.D2 mice were immunized once with plasmid pCMV-S. Mice received 500 μg of anti-CD25 mAb injected intraperitoneally 3 d before DNA immunization to deplete CD25+ cells. Induction of HBV-specific CD8+ T cells in peripheral blood mononuclear cells (PBMCs) was measured by S28-39 peptide loaded DimerX staining and their function was analyzed by intracellular IFN-γ staining. RESULTS: DNA immunization induced HBV-specific CD8+ T cells. At the peak T cell response (d 10), 7.1±2.0% of CD8+ T cells were HBV-specific after DNA immunization, whereas 12.7±3.2% of CD8+ T cells were HBV-specific in Treg-depleted mice, suggesting that DNA immunization induced more antigen-specific CD8+ T cells in the absence of CD25+ Treg cells (n = 6, P<0.05). Similarly, fewer HBV specific memory T cells were detected in the presence of these cells (1.3±0.4%) in comparison to Treg-depleted mice (2.6±0.9%) on d 30 after DNA immunization (n - 6, P<0.01). Both IFN-γ production and the avidity of the HBV-specific CD8+ T cell response to antigen were higher in HBV-specific CD8+ T cells induced in the absence of Treg cells. CONCLUSION: CD25+ Treg cells suppress priming and/or expansion of antigen-specific CD8+ T cells during DNA immunization and the peak CD8+ T cell response is enhanced by depleting this cell population. Furthermore, Treg cells appear to be involved in the contraction phase of the CD8+ T cell response and may affect the quality of memory T cell pools. The elimination of Treg cells or their inhibition may be important in immunot展开更多
Most land plants form symbiotic associations with arbuscular mycorrhizal （AM） fungi. These are the most common and widespread terrestrial plant symbioses, which have a global impact on plant mineral nutrition. The e...Most land plants form symbiotic associations with arbuscular mycorrhizal （AM） fungi. These are the most common and widespread terrestrial plant symbioses, which have a global impact on plant mineral nutrition. The establishment of AM symbiosis involves recognition of the two partners and bidirectional transport of different mineral and carbon nutrients through the symbiotic interfaces within the host root cells. Intrigu- ingly, recent discoveries have highlighted that lipids are transferred from the plant host to AM fungus as a major carbon source, in this review, we discuss the transporter-mediated transfer of carbon, nitrogen, phosphate, potassium and sulfate, and present hypotheses pertaining to the potential regulatory mecha- nisms of nutrient exchange in AM symbiosis. Current challenges and future perspectives on AM symbiosis research are also discussed.展开更多
Objective:To detect the inhibiting co-stimulating molecule CTLA4 and cytokines secreted by Treg cells, and explore the immunology mechanism of T regulatory cells acting on effector T cells in co-cultured system(CCS) a...Objective:To detect the inhibiting co-stimulating molecule CTLA4 and cytokines secreted by Treg cells, and explore the immunology mechanism of T regulatory cells acting on effector T cells in co-cultured system(CCS) and separating-cultured system(SCS). Methods: Detecting the percentage of CTLA4 and CD28 expressed on the Treg cells and effector T cells, and then adding Treg cells to mixed lymphocyte reaction(MLR) system in CCS and TransWell Millicell-PCF SCS, at the same time, adding or not adding anti-IL-10 or anti-TGF-β1 to the reacting systems, examining the inhibitory capacity of Treg cells exerting on the MLR. Results: Compared with effector T cells, Treg cells expressed higher level CTLA4 and secreted much more IL-10 and TGF-β1(P<0.01). The inhibitory capacity of Treg cells co-cultured with effector T cells is much stronger than that in separating cultured group(P<0.01). Moreover, the inhibiting rate of Treg cells exerting on effector T cells through secreting IL-10 was more powerful than that through secreting TGF-β1(P<0.01). Conclusion: Both cell-to-cell contact and cytokines secretion mechanisms are involved in CD4 +CD25 + Treg cells operating function. However, the former is more important. Intrestingly, we for the first time point found that IL-10 plays more powerful roles than TGF-β1 in the cytokines secretion mechanism.展开更多
文摘Background Recent recognition is that Th2 response is insufficient to fully explain the aetiology of asthma. Other CD4^＋ T cells subsets might play a role in asthma. We investigated the relative abundance and activities of Thl, Th2, Th17 and CD4^＋CD25^＋ Treg cells in patients with allergic asthma. Methods Twenty-two patients with mild asthma, 17 patients with moderate to severe asthma and 20 healthy donors were enrolled. All patients were allergic to house dust mites. Plasma total IgE, pulmonary function and Asthma Control Questionnaire were assessed. The proportions of peripheral blood Thl, Th2, Th17 and CD4^＋CD25^＋ Treg cells were determined by flow cytometry. The expression of cytokines in plasma and Jn the culture supernatant of peripheral blood mononuclear cells was determined by enzyme linked, immunosorbent assay. Results The frequency of blood Th2 cells and IL-4 levels in plasma and culture supernatant of peripheral blood mononuclear cells were increased in all patients with allergic asthma. The frequency of Th17 cells and the plasma and culture supernatant levels of IL-17 were increased, whereas the frequency of CD4^＋CD25^＋ Treg cells and plasma IL-10 levels were decreased in patients with moderate to severe asthma. Dermatophagoides pteronyssinus specific IgE levels were positively correlated with the percentage of blood Th2 cells and plasma IL-4 levels. Forced expiratory volume in the first second was negatively correlated with the frequency of Th17 cells and plasma IL-17 levels, and positively correlated with the frequency of Treg cells. However, mean Asthma Control Questionnaire scores were positively correlated with the frequency of Th17 cells and plasma IL-17 levels, and negatively correlated with the frequency of Treg cells. Conclusions Imbalances in Thl/Th2 and Th17/Treg were found in patients with allergic asthma. Furthermore, elevated Th17 cell responses, the absence of Tregs and an imbalance in Th17/Treg levels were associated with moderate to severe asthma.
基金the National Natural Science Foundation of China,No.81373143 and No.81571535 to Tu ZKKey Projects of Basic Research and Applied Basic Research in Universities of Guangdong Province,No.2018KZDXM055 to Tu ZK
文摘Hepatitis B virus(HBV) infection is one the leading risk factors for chronic hepatitis, liver fibrosis, cirrhosis and hepatocellular cancer(HCC), which are a major global health problem. A large number of clinical studies have shown that chronic HBV persistent infection causes the dysfunction of innate and adaptive immune response involving monocytes/macrophages, dendritic cells, natural killer(NK) cells, T cells. Among these immune cells, cell subsets with suppressive features have been recognized such as myeloid derived suppressive cells(MDSC),NK-reg, T-reg, which represent a critical regulatory system during liver fibrogenesis or tumourigenesis. However, the mechanisms that link HBVinduced immune dysfunction and HBV-related liver diseases are not understood.In this review we summarize the recent studies on innate and adaptive immune cell dysfunction in chronic HBV infection, liver fibrosis, cirrhosis, and HCC, and further discuss the potential mechanism of HBV-induced immunosuppressive cascade in HBV infection and consequences. It is hoped that this article will help ongoing research about the pathogenesis of HBV-related hepatic fibrosis and HBV-related HCC.
文摘Background Astragalus polysaccharides （APS）, the main active extract from Astragalus membranaceus （a traditional Chinese medicinal herb）, is associated with a variety of immunomodulatory activities. The purpose of the present study was to examine the effect of APS on the function of Treg cells in the tumor microenvironment of human hepatocellular carcinoma （HCC） and to identify the pharmacologic mechanism of APS responsible for the anti-chemotactic activity in CD4＋CD25^highTreq cells in tumor site of HCC.
文摘Hepatocellular carcinoma (HCC) is one of the most com- mon cancers in the world with an annual incidence of more than 500 000 in the year 2000. Its incidence is rising in many countries. Recently, it has been estimated that about 53% of HCC cases in the world are related to hepatitis B virus (HBV). The epidemiological association of HBV with HCC is well established. In recent studies, it was revealed that HBsAg carriers have a 25-37 times increased risk of developing HCC as compared to non-infected people. At present, HBV-associated carcinogenesis can be seen as a multi-factorial process that includes both direct and indirect mechanisms that might act synergistically. The integration of HBV DNA into the host genome occurs at early steps of clonal tumor expansion. The integration has been shown in a number of cases to affect a variety of cancer- related genes and to exert insertional mutagenesis. The permanent liver inflammation, induced by the immune response, resulting in a degeneration and regeneration process confers to the accumulation of critical mutations in the host genome. In addition to this, the regulatory proteins HBx and the PreS2 activators that can be encoded by the integrate exert a tumor promoter-like function resulting in positive selection of cells producing a functional regulatory protein. Gene expression profiling and proteomic techniques may help to characterize the molecular mechanisms driving HBV-associated carcino- genesis, and thus potentially identify new strategies in diagnosis and therapy.
文摘Background and objective： Umbilical cord （UC）-derived mesenchymal stem cells （MSCs） have shown immunoregulation of various immune cells. The aim of this study was to investigate the mechanism of UC MSCs in the regulation of peripheral regulatory T cells （Treg） and T helper 17 （Th17） cells in patients with systemic lupus erythematosus （SLE）. Methods： Thirty patients with active SLE, refractory to conventional therapies, were given UC MSCs infusions. The percentages of peripheral blood CD4＋CD25＋Foxp3＋ regulatory T cells （Treg） and CD3＋CD8-1L17A＋ Th17 cells and the mean fluorescence intensities （MFI） of Foxp3 and IL- 17 were measured at I week, I month, 3 months, 6 months, and 12 months after MSCs transplantation （MSCT）. Serum cytokines, including transforming growth factor beta （TGF-β）, tumor necrosis factor alpha （TNF-α）, interleukin 6 （IL-6）, and IL-17A were detected using ELISA. Peripheral blood mononuclear cells from patients were collected and co-cultured with UC MSCs at ratios of 1：1, 10：1, and 50：1, respectively, for 72 h to detect the proportions of Treg and Th17 cells and the MFIs of Foxp3 and IL-17 were determined by flow cytometry. The cytokines in the supernatant solution were detected using ELISA. Inhibitors targeting TGF-β, IL-6, indoleamine 2,3-dioxygenase （IDO）, and prostaglandin E2 were added to the co-culture system, and the percentages of Treg and Th17 cells were observed. Results： The percentage of peripheral Treg and Foxp3 MFI increased 1 week, 1 month, and 3 months after UC MSCs transplantation, while the Th17 proportion and MFI of IL-17 decreased 3 months, 6 months, and 12 months after the treatment, along with an increase in serum TGF-β at I week, 3 months, and 12 months and a decrease in serum TNF-a beginning at I week. There were no alterations in serums IL-6 and IL-17A before or after MSCT. In vitro studies showed that the UC MSCs dose-dependently up-regulated peripheral Treg proportion in SLE patients, which was no
文摘The balance between immune effector cells and immunosuppressive cells and how this regulates the tumor microenvironment has been well described.A significant contribution of immune regulatory cells,including regulatory T cells,to tumor progression has been widely reported.An emerging body of evidence has recently recognized a role for B cells in modulating the immune response to tumors and lymphoid malignancies.Regulatory B cells(Bregs)are a newly designated subset of B cells that have been shown to play a pivotal role in regulating immune responses involved in inflammation,autoimmunity and,more recently,cancer.Bregs can suppress diverse cell subtypes,including T cells,through the secretion of anti-inflammatory mediators,such as IL-10,and can facilitate the conversion of T cells to regulatory T cells,thus attenuating anti-tumor immune responses.Similar B-cell subpopulations have been reported to be recruited to the tumor but to acquire their immunosuppressive properties within the tumor bed and thereby attenuate anti-tumor immune responses.However,despite a pivotal role for Bregs in promoting inflammation and carcinogenesis,the phenotypic diversity of the cell surface markers that are unique to Bregs remains unclear in mice and humans.In this review,we summarize the characteristics of Bregs and review our current knowledge of Bregs and their inhibition of anti-tumor immune responses in murine tumor models and cancer patients.
基金This work was supported by grants from the National Natural Science Foundation for Distinguished Young Scholars(C03020504,Y.Z.)the National Basic Research Program(973 Program,2003CB515501,Y.Z.)+2 种基金100 Quality Vocational Colleges of Chinese Academy of Sciences(2003-85,Y.Z.)the Knowledge Innovation Program of Chinese Academy of Sciences(KSCX2-SW-333,Y.Z.)the Scientific Research Foundation for the Returned 0verseas Chinese Scholars of State Education Ministry(2005-546,Y.Z.).
文摘The homeostasis of the immune system depends on the balance between the immune response to an invaded pathogen and the immune tolerance to self antigens. Both central and peripheral tolerances are important mechanisms for the induction and maintenance of T cell tolerance. Recently, much attention has been paid to regulatory T cells （Treg）, which play a significant role in maintaining peripheral immune tolerance. So far, there has been no satisfactory advance regarding the surface markers of Treg cells, as none is unique for Treg cells. In this review, we summarize some important molecules expressed in naturally occurring CD4^＋CD25^＋ Treg cells （nTreg）, including forkhead/winged-helix family transcriptional repressor p3 （Foxp3）, the tumor necrosis factor receptor （TNFR） family, CD28/CTLA4 molecules, chemokine receptors, Toll-like receptors （TLRs）, membrane- bound TGF-β and other molecules, such as neuropilin-1, lymphocyte activation gene-3 （LAG）-3 and granzyme. This review provides a collective view on current studies of nTreg cell activation and development related to the expression of molecules and cell phenotype markers, which is important for elucidation of nTreg cell origin, development and function. Cellular ＆ Molecular Immunology. 2006;3（3）：189-195.
基金This work was supported by the National Key Research Program of China(No.2006CB944007,to DJL)the National Natural Science Foundation of China(No.30801502,to LW)+1 种基金the Shanghai Leading Academic Discipline Project B117(to DJL)the Program for Outstanding Medical Academic Leaders(to DJL).
文摘Cross-talk has been shown to occur between the immune system and bone metabolism pathways.In the present study,we investigated the impact of CD4^(+)CD25^(+)Foxp3^(+) regulatory T(Treg)cells on osteoclastogenesis and bone resorption.Treg cells that were isolated and purified from peripheral blood mononuclear cells(PBMCs)of healthy adults inhibited both the differentiation of osteoclasts(OCs)from human embryo bone marrow cells(BMCs)and the pit formation in a dose-dependent manner.In cell cocultures,the production levels of both interleukin-10(IL-10)and transforming growth factor-beta 1(TGF-β1)were proportionally upregulated as the ratio of Treg cells to BMCs was increased,and the inhibition of OC differentiation and bone resorption by Treg cells was completely reversed by anti-IL-10 and anti-TGF-β1 antibodies.Treatment of BMC and Treg cell cocultures with 17β-estradiol(E2)at concentrations between 10^(-7) and 10^(-9) mol/l suppressed OC differentiation and bone resorption more efficiently than it did in cultures of BMCs alone;this enhanced suppression occurred via the stimulation of Treg cell IL-10 and TGF-b1 expression.These data suggest that Treg cells suppress OC differentiation and bone resorption by secreting IL-10 and TGF-β1.E2 enhances the suppressive effects of Treg cells on OC differentiation and bone resorption by stimulating IL-10 and TGF-β1 secretion from these cells.Therefore,Treg cell-derived IL-10 and TGF-b1 are likely involved in the regulation of E2 on bone metabolism and represent potential therapeutic targets for the treatment of postmenopausal osteoporosis(PMO).
基金Supported by The Major National Science and Technology Projects for Infectious Diseases (11th and 12th Five Year, China),No. 2008ZX10002-007, No. 2012ZX10002-007the Foundation of Shaanxi Provincial Science and Technology Plan Projects,No. 2011K14-09-09
文摘AIM: To investigate the role of T helper 17 cells (Th17) and regulatory T cells (Treg) in hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF).METHODS: We enrolled 79 patients with HBV infection into the study, 50 patients with HBV-related ACLF and 29 patients with chronic hepatitis B (CHB), from the First Affiliated Hospital of Medical College from January 2009 to June 2012. The ACLF patients were diagnosed according to the criteria recommended by The 19th Conference of the Asian Pacific Association for the Study of the Liver in 2009. Twenty healthy individuals with a similar gender and age structures to the two patient groups were also included as the normal controls (NC). Of the 50 ACLF patients, 28 were subsequently classified as non-survivors: 19 patients died from multiorgan failure, 3 underwent liver transplantation, and 6 discontinued therapy during follow-up because of financial reasons. The remaining 22 ACLF patients whose liver and anticoagulation function recovered to nearly normal levels within the next 6 mo were classified as survivors. The number of circulating Treg and Th17 cells was determined upon diagnosis and during the 8th week of follow-up through flow cytometry. RESULTS: The percentage of circulating Treg cells in the ACLF group was significantly higher than that in the CHB group (5.50% ± 1.15% vs 3.30% ± 1.13%, P < 0.01). The percentages of circulating Th17 cells in the ACLF and the CHB groups were significantly higher than that in the NC group (6.32% ± 2.22% vs 1.56% ± 0.44%, P < 0.01; 3.53% ± 1.65% vs 1.56% ± 0.44%, P < 0.01). No significant difference in Treg cell to Th17 cell ratio was observed between the ACLF group and the CHB group (0.98 ± 0.44 vs 1.12 ± 0.64, P = 0.991), whereas those in the two HBV infection groups were significantly lower than that in the NC group (1.85 ± 1.22; both P < 0.01). The percentage of Treg cells in the survivors during the 8th week of follow-up was significantly lower than that during peak ACLF severity [total bilirubin (TBIL)
文摘B cells are generally considered to be positive regulators of the immune response because of their capability to produce antibodies, including autoantibodies. The production of antibodies facilitates optimal CD4＋ T-cell activation because B cells serve as antigen-presenting cells and exert other modulatory functions in immune responses. However, certain B cells can also negatively regulate the immune response by producing regulatory cytokines and directly interacting with pathogenic T cells via cell-to-cell contact. These types of B Cells are defined as regulatory B （Breg） cells. The regulatory function of Breg cells has been demonstrated in mouse models of inflammation, cancer, transplantation, and particularly in autoimmunity. In this review, we focus on the recent advances that lead to the understanding of the development and function of Breg cells and the implications of B cells in human autoimmune diseases.
基金Supported by in part Grant-in-Aid for Scientific Research (C) (toK.K)
文摘AIM: Persistent hepatitis B virus (HBV) infection is characterized by a weak CD8+ T cell response to HBV. Immunotherapeutic strategies that overcome tolerance and boost these suboptimal responses may facilitate viral clearance in chronically infected individuals. Therefore, we examined whether CD25+CD4+ regulatory T (Treg) cells might be involved in a inhibition of CD8+T cell priming or in the modulation of the magnitude of the 'peak' antiviral CD8+ T cell response primed by DNA immunization. METHODS: B10.D2 mice were immunized once with plasmid pCMV-S. Mice received 500 μg of anti-CD25 mAb injected intraperitoneally 3 d before DNA immunization to deplete CD25+ cells. Induction of HBV-specific CD8+ T cells in peripheral blood mononuclear cells (PBMCs) was measured by S28-39 peptide loaded DimerX staining and their function was analyzed by intracellular IFN-γ staining. RESULTS: DNA immunization induced HBV-specific CD8+ T cells. At the peak T cell response (d 10), 7.1±2.0% of CD8+ T cells were HBV-specific after DNA immunization, whereas 12.7±3.2% of CD8+ T cells were HBV-specific in Treg-depleted mice, suggesting that DNA immunization induced more antigen-specific CD8+ T cells in the absence of CD25+ Treg cells (n = 6, P<0.05). Similarly, fewer HBV specific memory T cells were detected in the presence of these cells (1.3±0.4%) in comparison to Treg-depleted mice (2.6±0.9%) on d 30 after DNA immunization (n - 6, P<0.01). Both IFN-γ production and the avidity of the HBV-specific CD8+ T cell response to antigen were higher in HBV-specific CD8+ T cells induced in the absence of Treg cells. CONCLUSION: CD25+ Treg cells suppress priming and/or expansion of antigen-specific CD8+ T cells during DNA immunization and the peak CD8+ T cell response is enhanced by depleting this cell population. Furthermore, Treg cells appear to be involved in the contraction phase of the CD8+ T cell response and may affect the quality of memory T cell pools. The elimination of Treg cells or their inhibition may be important in immunot
文摘Most land plants form symbiotic associations with arbuscular mycorrhizal （AM） fungi. These are the most common and widespread terrestrial plant symbioses, which have a global impact on plant mineral nutrition. The establishment of AM symbiosis involves recognition of the two partners and bidirectional transport of different mineral and carbon nutrients through the symbiotic interfaces within the host root cells. Intrigu- ingly, recent discoveries have highlighted that lipids are transferred from the plant host to AM fungus as a major carbon source, in this review, we discuss the transporter-mediated transfer of carbon, nitrogen, phosphate, potassium and sulfate, and present hypotheses pertaining to the potential regulatory mecha- nisms of nutrient exchange in AM symbiosis. Current challenges and future perspectives on AM symbiosis research are also discussed.
文摘Objective:To detect the inhibiting co-stimulating molecule CTLA4 and cytokines secreted by Treg cells, and explore the immunology mechanism of T regulatory cells acting on effector T cells in co-cultured system(CCS) and separating-cultured system(SCS). Methods: Detecting the percentage of CTLA4 and CD28 expressed on the Treg cells and effector T cells, and then adding Treg cells to mixed lymphocyte reaction(MLR) system in CCS and TransWell Millicell-PCF SCS, at the same time, adding or not adding anti-IL-10 or anti-TGF-β1 to the reacting systems, examining the inhibitory capacity of Treg cells exerting on the MLR. Results: Compared with effector T cells, Treg cells expressed higher level CTLA4 and secreted much more IL-10 and TGF-β1(P<0.01). The inhibitory capacity of Treg cells co-cultured with effector T cells is much stronger than that in separating cultured group(P<0.01). Moreover, the inhibiting rate of Treg cells exerting on effector T cells through secreting IL-10 was more powerful than that through secreting TGF-β1(P<0.01). Conclusion: Both cell-to-cell contact and cytokines secretion mechanisms are involved in CD4 +CD25 + Treg cells operating function. However, the former is more important. Intrestingly, we for the first time point found that IL-10 plays more powerful roles than TGF-β1 in the cytokines secretion mechanism.
