The intestinal immune system maintains a delicate balance between immunogenicity against invading pathogens and tolerance of the commensal microbiota.Inflammatory bowel disease(IBD)involves a breakdown in tolerance to...The intestinal immune system maintains a delicate balance between immunogenicity against invading pathogens and tolerance of the commensal microbiota.Inflammatory bowel disease(IBD)involves a breakdown in tolerance towards the microbiota.Dendritic cells(DC),macrophages(MΦ)and B-cells are known as professional antigen-presenting cells(APC)due to their specialization in presenting processed antigen to T-cells,and in turn shaping types of T-cell responses generated.Intestinal DC are migratory cells,unique in their ability to generate primary T-cell responses in mesenteric lymph nodes or Peyer’s patches,whilst MΦand B-cells contribute to polarization and differentiation of secondary T-cell responses in the gut lamina propria.The antigen-sampling function of gut DC and MΦenables them to sample bacterial antigens from the gut lumen to determine types of T-cell responses generated.The primary function of intestinal B-cells involves their secretion of large amounts of immunoglobulin A,which in turn contributes to epithelial barrier function and limits immune responses towards to microbiota.Here,we review the role of all three types of APC in intestinal immunity,both in the steady state and in inflammation,and how these cells interact with one another,as well as with the intestinal microenvironment,to shape mucosal immune responses.We describe mechanisms of maintaining intestinal immune tolerance in the steady state but also inappropriate responses of APC to components of the gut microbiota that contribute to pathology in IBD.展开更多
Porcine reproductive and respiratory syndrome(PRRS) is one of the most important diseases of swine industry. The causal agent, PRRS-virus(PRRSV), is able to evade the host immune response and survive in the organism c...Porcine reproductive and respiratory syndrome(PRRS) is one of the most important diseases of swine industry. The causal agent, PRRS-virus(PRRSV), is able to evade the host immune response and survive in the organism causing transient infections. Despite all scientific efforts, there are still some gaps in the knowledge of the pathogenesis of this disease. Antigen presenting cells(APCs), as initiators of the immune response, are located in the first line of defense against microorganisms, and are responsible for antigen recognition, processing and presentation. Dendritic cells(DCs) are the main type of APC involved in antigen presentation and they are susceptible to PRRSV infection. Thus, PRRSV replication in DCs may trigger off different mechanisms to impair the onset of a host effective immune response against the virus. On the one side, PRRSV may impair the basic functions of DCs by regulating the expression of major histocompatibility complex class Ⅱ and CD80/86. Other strategy followed by the virus is the induction of cell death of APCs by apoptosis, necrosis or both of them. The impairment and/or cell death ofAPCs could lead to a failure in the onset of an efficient immune response, as long as cells could not properly activate T cells. Future aspects to take into account are also discussed in this review.展开更多
AIM:To study the effects of probiotic metabolites on maturation stage of antigen-presenting immune cells.METHODS:Ganeden Bacillus coagulans 30(GBC30) bacterial cultures in log phase were used to isolate the secreted m...AIM:To study the effects of probiotic metabolites on maturation stage of antigen-presenting immune cells.METHODS:Ganeden Bacillus coagulans 30(GBC30) bacterial cultures in log phase were used to isolate the secreted metabolite(MET) fraction.A second fraction was made to generate a crude cell-wall-enriched fraction,by centrifugation and lysis,followed by washing.A preparation of MET was subjected to size exclusion centrifugation,generating three fractions:< 3 kDa,3-30 kDa,and 30-200 kDa and activities were tested in comparison to crude MET and cell wall in primary cultures of human peripheral blood mononuclear cell(PBMC) as a source of antigen-presenting mononuclear phagocytes.The maturation status of mononuclear phagocytes was evaluated by staining with monoclonal antibodies towards CD14,CD16,CD80 and CD86 and analyzed by flow cytometry.RESULTS:Treatment of PBMC with MET supported maturation of mononuclear phagocytes toward both macrophage and dendritic cell phenotypes.The biological activity unique to the metabolites included a reduction of CD14+ CD16+ pro-inflammatory cells,and this property was associated with the high molecular weight metabolite fraction.Changes were also seen for the dendritic cell maturation markers CD80 and CD86.On CD14dim cells,an increase in both CD80 and CD86 expression was seen,in contrast to a selective increase in CD86 expression on CD14bright cells.The co-expression of CD80 and CD86 indicates effective antigen presentation to T cells and support of T helper cell differentiation.The selective expression of CD86 in the absence of CD80 points to a role in generating T regulatory cells.CONCLUSION:The data show that a primary mechanism of action of GBC30 metabolites involves support of more mature phenotypes of antigen-presenting cells,important for immunological decision-making.展开更多
AIM:To investigate the anti-inflammatory effects of cinnamon extract and elucidate its mechanisms for targeting the function of antigen presenting cells.METHODS:Cinnamon extract was used to treat murine macrophage cel...AIM:To investigate the anti-inflammatory effects of cinnamon extract and elucidate its mechanisms for targeting the function of antigen presenting cells.METHODS:Cinnamon extract was used to treat murine macrophage cell line(Raw 264.7),mouse primary antigen-presenting cells(APCs,MHCII+) and CD11c+dendritic cells to analyze the effects of cinnamon extract on APC function.The mechanisms of action of cinnamon extract on APCs were investigated by analyzing cytokine production,and expression of MHC antigens and co-stimulatory molecules by quantitative real-time PCR and flow cytometry.In addition,the effect of cinnamon extract on antigen presentation capacity and APC-dependent T-cell differentiation were analyzed by [H3]-thymidine incorporation and cytokine analysis,respectively.To confirm the anti-inflammatory effects of cinnamon extract in vivo,cinnamon or PBS was orally administered to mice for 20 d followed by induction of experimental colitis with 2,4,6 trinitrobenzenesulfonic acid.The protective effects of cinnamon extract against experimental colitis were measured by checking clinical symptoms,histological analysis and cytokine expression prof iles in inflamed tissue.RESULTS:Treatment with cinnamon extract inhibited maturation of MHCII+ APCs or CD11c+ dendritic cells(DCs) by suppressing expression of co-stimulatory molecules(B7.1,B7.2,ICOS-L),MHCII and cyclooxygenase(COX)-2.Cinnamon extract induced regulatory DCs(rDCs) that produce low levels of pro-inflammatory cytokines [interleukin(IL)-1β,IL-6,IL-12,interferon(IFN)-γ and tumor necrosis factor(TNF)-α] while expressing high levels of immunoregulatory cytokines(IL-10 and transforming growth factor-β).In addition,rDCs generated by cinnamon extract inhibited APC-dependent T-cell proliferation,and converted CD4+ T cells into IL-10high CD4+ T cells.Furthermore,oral administration of cinnamon extract inhibited development and progression of intestinal colitis by inhibiting expression of COX-2 and pro-inflammatory cytokines(IL-1β,IFN-γ and TNF-α),while enhancing IL-10 levels.CONCLUSION:Our study suggests the potential of cinnamon extract as an anti-inflammatory agent by targeting the generation of regulatory APCs and IL-10+ regulatory T cells.展开更多
BACKGROUND: The antigen reducing ability of dentritic cells (DCs), a kind of antigen presenting cells (APCs) initiating immune response, is associated with the specific immune tolerance of chronic hepatitis B(CHB) pat...BACKGROUND: The antigen reducing ability of dentritic cells (DCs), a kind of antigen presenting cells (APCs) initiating immune response, is associated with the specific immune tolerance of chronic hepatitis B(CHB) patients. However, the dysfunction of DCs can be possibly reversed by the stimulation of antigen peptides. In this study, DCs were cultured from peripheral blood monocytes (PBMCs) in patients with CHB in vitro, and the expression of phenotypic molecules on DCs loaded by different concentrations of HBsAg was observed. METHODS: Forty patients with CHB were divided randomly into 4 groups(10 patients in each group). PBMCs were isolated, and DCs were cultured after addition of granulocyte/macrophage colony-stimulating factor (GMCSF) and interleukin 4(IL-4). On the 9th day, DCs of the experimental groups were loaded at HBsAg concentrations of 2.5mg/L, 5mg/L and 10mg/L for 24 hours, whereas those of the control group were not loaded. An electron microscope was used to analyze the morphological changes of the DCs. The expression of phenotypic molecules on DCs in different groups was detected with flow cytometry. RESULTS: A combination of GM-CSF and IL-4 produced DCs from PBMCs in patients with CHB after being cultured for 9 days, whose morphological changes were tested by an electron microscope. The expression of phenotypic molecules on DCs in the control group was as low as CD83 (8.02±3.99)%, CD80(8.77±2.06)%, and MHC-DR (14.05±2.66)%. Loaded by different concentrations of HBsAg, the up-regulation of phenotypic molecules on DCs was found, with CD83(18.35±2.93)%, CD80(42.63±7.15)% and MHC-DR(47.49±6.59)% in 2.5mg/L HBsAg loading group, CD83(17.88±3.12)%, CD80(45.24± 10.93)% and MHC-DR(47.07±8.52)% in 5mg/L HBsAg loading group and CD83(16.74±2.86)%, CD80(44.59±6.99)% and MHC-DR(48.59±7.42)% in 10mg/L HBsAg loading group, respectively. Compared with the control group, the phenotypic molecules in the experimental groups were all different significantly (P<0.01), but among them, there were no differences (P>0.05). CONCLUSIONS: DCs cultured from PBMCs in the patients with CHB under the conditions of GM-CSF and IL-4 present on the typical dendritic morphology but are immature for expressing low phenotypic molecules. Loaded by different concentrations of HBsAg, the immature DCs can differentiate to mature DCs for expressing increasing phenotypic molecules.展开更多
Immune reactions to foreign or self-antigens lead to protective immunity and, sometimes, immune disorders such as allergies and autoimmune diseases. Antigen presenting cells (APC) including epidermal Langerhans cells ...Immune reactions to foreign or self-antigens lead to protective immunity and, sometimes, immune disorders such as allergies and autoimmune diseases. Antigen presenting cells (APC) including epidermal Langerhans cells (LCs) play an important role in the course and outcome of the immune reactions. Epidermal powder immunization (EPI) is a technology that offers a tool to manipulate the LCs and the potential to harness the immune reactions towards prevention and treatment of infectious diseases and immune disorders.展开更多
Bone marrow precursor cells were extracted from C57BL/6J mice aged 7-8 weeks, and dendritic cells were purified using anti-CD1 lc (a specific marker for dendritic cells) antibody-coated magnetic beads. Immunofluores...Bone marrow precursor cells were extracted from C57BL/6J mice aged 7-8 weeks, and dendritic cells were purified using anti-CD1 lc (a specific marker for dendritic cells) antibody-coated magnetic beads. Immunofluorescence staining revealed that the expression levels of endomorphin-1 and endomorphin-2 were upregulated in dendritic cells activated by lipopolysaccharide. An enzyme Jmmunoassay showed that lipopolysaccharide and other Toll-like receptor ligands promoted the secretion of endomorphin-1 and endomorphin-2 from activated dendritic cells. [3H]-thymidine incorporation demonstrated that endomorphin-1 and endomorphin-2 both inhibited the proliferation of T lymphocyte induced by activated dendritic cells. Furthermore, this immunosuppressive effect was blocked by CTOP, a specific antagonist of IJ-opioid receptors. Our experimental findings indicate that activated dendritic cells can induce the expression and secretion of endomorphins, and that endomorphins suppress T lymphocyte proliferation through activation of iJ-opioid receptors.展开更多
Background and Objectives Autoimmune reaction may play an important role in the pathogenesis and progress in virus myocarditis. Dendritic cells are the initiators of immune reaction to foreign antigens and are conside...Background and Objectives Autoimmune reaction may play an important role in the pathogenesis and progress in virus myocarditis. Dendritic cells are the initiators of immune reaction to foreign antigens and are considered to be key players in the induction and maintenance of autoimmune reactions. This study was undertaken to investigate the role of DC in mice with virus myocarditis. Methods and Results Fifty Balb/c mice were injected Coxsackie B3 virus to induce myocarditis and ten mice were injected culture liquid as control group. The hearts of virus - infected mice were harvested on day 3, 7, 14, 28 after the injection. All the hearts were sliced to do HE staining, MHC Ⅱ antigen and S - 100 protein immunohistochemical staining. The inflammation response and expression of MHC Ⅱ antigen and S - 100 protein positive stained cells were observed. The MHC Ⅱ antigen positive score were 1.42±0.95, 2.24 ±1. 00, 3. 23± 1. 16, 2. 58 ± 1. 05 respectively in group 3d, 7 d, 14 d, 28 d, which were significant different from control group(0. 50 ±0.75, P <0. 05). The S-100 positive staining cells in control group was 3. 2±1. 0. And the numbers were 6. 7 ± 1. 4 , 16. 4 ± 2. 5 , 21. 2±3. 3 , 13. 4 ± 2. 3 respectively in group 3 d, 7 d, 14 d, 28 d, and there were significant differences compared with the control group ( P < 0. 01) . Conclusions Immune reaction was involved in the pathogenesis in Coxsackie B3 virus - induced myocarditis in mouse, and dendritic cell might play an important role in the immune reaction.展开更多
<p style="text-align:justify;"> <span>Following organ transplantation</span><span>,</span><span> the outcome of the encounter between an APC and a T lymphocyte is str...<p style="text-align:justify;"> <span>Following organ transplantation</span><span>,</span><span> the outcome of the encounter between an APC and a T lymphocyte is strongly dependent on the presence of costimulatory and co-inhibitory molecules, the former associated with allograft rejection and the latter with allograft acceptance. We evaluated the expression of PD-L2, GITR, ILT-2/3/5, and ILT-4 on graft-infiltrating cells procured by Fnab from human KTx under different immunosuppressive regimens. Methods: Fnab biopsies were performed on days 7 or 14</span><span> </span><span>-</span><span> </span><span>30 in stable KTx and on the day of acute rejection diagnosis. Cytopreparations were studied by the enzymatic avidin biotin complex staining. Results: Acute rejection group </span><span>showed a significant down-regulated expression of PD-L2, GITR, and ILT-2/3/5 </span><span>as compared to stable group, while for ILT-4 we did not find significant difference. Anti-IL2</span><i><span>α</span></i><span>R and rapamicyn treatment trend to down-regulate ILT-4 expression, although meaningless. A significant</span><span>ly</span><span> positive correlation was observed between PD-L2 and GITR expression in Fnab. The PPV for acute rejection diagnosis for both PD-L2 and GITR w</span><span>as</span><span> clearly above 0.8. Conclusions: Our findings point to an early entrance of cells expressing PD-L2, GITR and ILT-2/3/5 inside human KTx who are going to remain rejection-free. Both PD-L2 and GITR shared a high ability to rule-in and rule-out acute rejection.</span> </p>展开更多
Rheumatoid arthritis is an autoimmune disease that primarily affects the limbs, but the pathogenic mechanism remains unclear. 78 T cells, a T-cell subpopulation, are characterized by multiple biological functions and ...Rheumatoid arthritis is an autoimmune disease that primarily affects the limbs, but the pathogenic mechanism remains unclear. 78 T cells, a T-cell subpopulation, are characterized by multiple biological functions and associated with a variety of diseases. This study investigated the antigen-presenting effects of γδ2 cells and their relationship with rheumatoid arthritis development. We found that Vγ9Vδ2 T cells (the predominant subtype of γδ T cells in peripheral blood) were activated by isopentenyl pyrophosphate to continuously proliferate and differentiate into effector memory cells. The effector memory Vγ9Vδ2 T cells exhibited phenotypic characteristics of specific antigen-presenting cells, including high HLA-DR and CD80/86 expression. These Vγ9Vδ2 T cells could present soluble antigens and synthetic peptides to CD4+ T cells. Vγ9Vδ2 T cells with different phenotypes showed different cytokine secretion patterns. Effector memoryVγ9Vδ2 T cells simultaneously secreted not only interferon (IFN)-γbut also IL-17. The peripheral blood and joint synovial fluid from RA patients contained numerous heterogeneous γδ T cells that were predominantly effector memory Vγ9Vδ2 T cells with the ability to secrete inflammatory factors. We also found that γδ T cells had a similar antigen-presenting capability to B cells. These results suggest that during the development of rheumatoid arthritis, 78 T cells can aggravate immune dysfunction and produce abnormal immune damage by secreting cytokines and inducing inflammatory cells to participate in synergistic inflammatory responses. Furthermore, γδ T cells can behave similarly to B cells to present viral peptides and autoantigen peptides to CD4+ T cells, thus sustaining CD4+ T-cell activation.展开更多
Artificial antigen-presenting cells are expected to stimulate the expansion and acquisition of optimal therapeutic features of T cells before infusion. Here CD32 that binds to a crystallizable fragment of IgG monoclon...Artificial antigen-presenting cells are expected to stimulate the expansion and acquisition of optimal therapeutic features of T cells before infusion. Here CD32 that binds to a crystallizable fragment of IgG monoclonal antibody was genetically expressed on human K562 leukemia cells to provide a ligand for T-cell receptor. CD86 and 4-1BBL, which are ligands of co-stimulating receptors of CD28 and 4-1BB, respectively, were also expressed on K562 cells. Then we accomplished the artificial antigen-presenting cells by coupling K32/CD86/4-1BBL cell with OKT3 monoclonal antibody against CD3, named K32/CD86/4-1BBL/OKT3 cells. These artificial modified cells had the abilities of inducing CD8^+ T cell activation, promoting CD8^+ T cell proliferation, division, and long-term growth, inhibiting CD8^+ T cell apoptosis, and enhancing CD8^+ T cell secretion of IFN-T and perforin. Furthermore, antigen-specific cytotoxic T lymphocytes could be retained in the culture stimulated with K32/CD86/4-1BBL/OKT3 cells at least within 28 days. This approach was robust, simple, reproducible and economical for expansion and activation of CD8^+ T cells and may have important therapeutic implications for adoptive immunotherapy. Cellular & Molecular Immunology.展开更多
Background The mechanism of chronic immune activation and impairment of HIV-specific immune responses during chronic infection is not fully understood. However, it is known that high immune activation leads to more ra...Background The mechanism of chronic immune activation and impairment of HIV-specific immune responses during chronic infection is not fully understood. However, it is known that high immune activation leads to more rapid progression to AIDS. We hypothesize that CD4^+ T cell-mediated viral antigen presentation contributes to this pathologic immune activation in HIV-infected individuals. Methods HIV-specific T cells, responding to noninfectious HIV-1 virions as antigen, were measured by flow cytometric assays. These experimental conditions reflect the in vivo condition where noninfectious HIV-1 represents more than 99% of the antigens. Results CD4^+ T cells purified from HIV-infected individuals were capable of cross presenting exogenous noninfectious HIV-1 virions to HIV-1-specific CD8^+ T cells. Cross presentation required the entry of HIV-1 to CD4^+ T cells and antigen translocation from endoplasmic reticulum to the Golgi complex. Blocking CD4^+ mediated activation of HIV-specific CD8^+ T cells and redirecting the viral antigens to antigen presenting cells improved HIV-specific T cell responses. Contusions One possible cause of chronic immune activation and impairment of HIV-1 specific T cell responses is represented by HIV-1 harboring CD4^+ T cells cross presenting HIV-1 antigen to activate CD8^+ T cells. This new mechanism provides the first evidence that cross presentation of noninfectious HIV-1 virions play a role in the immunopathogenesis of HIV-1 infection.展开更多
文摘The intestinal immune system maintains a delicate balance between immunogenicity against invading pathogens and tolerance of the commensal microbiota.Inflammatory bowel disease(IBD)involves a breakdown in tolerance towards the microbiota.Dendritic cells(DC),macrophages(MΦ)and B-cells are known as professional antigen-presenting cells(APC)due to their specialization in presenting processed antigen to T-cells,and in turn shaping types of T-cell responses generated.Intestinal DC are migratory cells,unique in their ability to generate primary T-cell responses in mesenteric lymph nodes or Peyer’s patches,whilst MΦand B-cells contribute to polarization and differentiation of secondary T-cell responses in the gut lamina propria.The antigen-sampling function of gut DC and MΦenables them to sample bacterial antigens from the gut lumen to determine types of T-cell responses generated.The primary function of intestinal B-cells involves their secretion of large amounts of immunoglobulin A,which in turn contributes to epithelial barrier function and limits immune responses towards to microbiota.Here,we review the role of all three types of APC in intestinal immunity,both in the steady state and in inflammation,and how these cells interact with one another,as well as with the intestinal microenvironment,to shape mucosal immune responses.We describe mechanisms of maintaining intestinal immune tolerance in the steady state but also inappropriate responses of APC to components of the gut microbiota that contribute to pathology in IBD.
基金Supported by The Spanish Ministry of Education and Science,No.AGL2009-12438/GAN
文摘Porcine reproductive and respiratory syndrome(PRRS) is one of the most important diseases of swine industry. The causal agent, PRRS-virus(PRRSV), is able to evade the host immune response and survive in the organism causing transient infections. Despite all scientific efforts, there are still some gaps in the knowledge of the pathogenesis of this disease. Antigen presenting cells(APCs), as initiators of the immune response, are located in the first line of defense against microorganisms, and are responsible for antigen recognition, processing and presentation. Dendritic cells(DCs) are the main type of APC involved in antigen presentation and they are susceptible to PRRSV infection. Thus, PRRSV replication in DCs may trigger off different mechanisms to impair the onset of a host effective immune response against the virus. On the one side, PRRSV may impair the basic functions of DCs by regulating the expression of major histocompatibility complex class Ⅱ and CD80/86. Other strategy followed by the virus is the induction of cell death of APCs by apoptosis, necrosis or both of them. The impairment and/or cell death ofAPCs could lead to a failure in the onset of an efficient immune response, as long as cells could not properly activate T cells. Future aspects to take into account are also discussed in this review.
基金Supported by A Research Sponsorship from Ganeden Biotech, Ohio,United States
文摘AIM:To study the effects of probiotic metabolites on maturation stage of antigen-presenting immune cells.METHODS:Ganeden Bacillus coagulans 30(GBC30) bacterial cultures in log phase were used to isolate the secreted metabolite(MET) fraction.A second fraction was made to generate a crude cell-wall-enriched fraction,by centrifugation and lysis,followed by washing.A preparation of MET was subjected to size exclusion centrifugation,generating three fractions:< 3 kDa,3-30 kDa,and 30-200 kDa and activities were tested in comparison to crude MET and cell wall in primary cultures of human peripheral blood mononuclear cell(PBMC) as a source of antigen-presenting mononuclear phagocytes.The maturation status of mononuclear phagocytes was evaluated by staining with monoclonal antibodies towards CD14,CD16,CD80 and CD86 and analyzed by flow cytometry.RESULTS:Treatment of PBMC with MET supported maturation of mononuclear phagocytes toward both macrophage and dendritic cell phenotypes.The biological activity unique to the metabolites included a reduction of CD14+ CD16+ pro-inflammatory cells,and this property was associated with the high molecular weight metabolite fraction.Changes were also seen for the dendritic cell maturation markers CD80 and CD86.On CD14dim cells,an increase in both CD80 and CD86 expression was seen,in contrast to a selective increase in CD86 expression on CD14bright cells.The co-expression of CD80 and CD86 indicates effective antigen presentation to T cells and support of T helper cell differentiation.The selective expression of CD86 in the absence of CD80 points to a role in generating T regulatory cells.CONCLUSION:The data show that a primary mechanism of action of GBC30 metabolites involves support of more mature phenotypes of antigen-presenting cells,important for immunological decision-making.
基金Supported by Grants from the BioGreen 21 Program, Rural Development Administration (PJ007054)Regional Technology Innovation Program of the MOCIE (RTI05-01-01)Korea Healthcare Technology R&D Project, Ministry of Health and Welfare (A080588-20)
文摘AIM:To investigate the anti-inflammatory effects of cinnamon extract and elucidate its mechanisms for targeting the function of antigen presenting cells.METHODS:Cinnamon extract was used to treat murine macrophage cell line(Raw 264.7),mouse primary antigen-presenting cells(APCs,MHCII+) and CD11c+dendritic cells to analyze the effects of cinnamon extract on APC function.The mechanisms of action of cinnamon extract on APCs were investigated by analyzing cytokine production,and expression of MHC antigens and co-stimulatory molecules by quantitative real-time PCR and flow cytometry.In addition,the effect of cinnamon extract on antigen presentation capacity and APC-dependent T-cell differentiation were analyzed by [H3]-thymidine incorporation and cytokine analysis,respectively.To confirm the anti-inflammatory effects of cinnamon extract in vivo,cinnamon or PBS was orally administered to mice for 20 d followed by induction of experimental colitis with 2,4,6 trinitrobenzenesulfonic acid.The protective effects of cinnamon extract against experimental colitis were measured by checking clinical symptoms,histological analysis and cytokine expression prof iles in inflamed tissue.RESULTS:Treatment with cinnamon extract inhibited maturation of MHCII+ APCs or CD11c+ dendritic cells(DCs) by suppressing expression of co-stimulatory molecules(B7.1,B7.2,ICOS-L),MHCII and cyclooxygenase(COX)-2.Cinnamon extract induced regulatory DCs(rDCs) that produce low levels of pro-inflammatory cytokines [interleukin(IL)-1β,IL-6,IL-12,interferon(IFN)-γ and tumor necrosis factor(TNF)-α] while expressing high levels of immunoregulatory cytokines(IL-10 and transforming growth factor-β).In addition,rDCs generated by cinnamon extract inhibited APC-dependent T-cell proliferation,and converted CD4+ T cells into IL-10high CD4+ T cells.Furthermore,oral administration of cinnamon extract inhibited development and progression of intestinal colitis by inhibiting expression of COX-2 and pro-inflammatory cytokines(IL-1β,IFN-γ and TNF-α),while enhancing IL-10 levels.CONCLUSION:Our study suggests the potential of cinnamon extract as an anti-inflammatory agent by targeting the generation of regulatory APCs and IL-10+ regulatory T cells.
文摘BACKGROUND: The antigen reducing ability of dentritic cells (DCs), a kind of antigen presenting cells (APCs) initiating immune response, is associated with the specific immune tolerance of chronic hepatitis B(CHB) patients. However, the dysfunction of DCs can be possibly reversed by the stimulation of antigen peptides. In this study, DCs were cultured from peripheral blood monocytes (PBMCs) in patients with CHB in vitro, and the expression of phenotypic molecules on DCs loaded by different concentrations of HBsAg was observed. METHODS: Forty patients with CHB were divided randomly into 4 groups(10 patients in each group). PBMCs were isolated, and DCs were cultured after addition of granulocyte/macrophage colony-stimulating factor (GMCSF) and interleukin 4(IL-4). On the 9th day, DCs of the experimental groups were loaded at HBsAg concentrations of 2.5mg/L, 5mg/L and 10mg/L for 24 hours, whereas those of the control group were not loaded. An electron microscope was used to analyze the morphological changes of the DCs. The expression of phenotypic molecules on DCs in different groups was detected with flow cytometry. RESULTS: A combination of GM-CSF and IL-4 produced DCs from PBMCs in patients with CHB after being cultured for 9 days, whose morphological changes were tested by an electron microscope. The expression of phenotypic molecules on DCs in the control group was as low as CD83 (8.02±3.99)%, CD80(8.77±2.06)%, and MHC-DR (14.05±2.66)%. Loaded by different concentrations of HBsAg, the up-regulation of phenotypic molecules on DCs was found, with CD83(18.35±2.93)%, CD80(42.63±7.15)% and MHC-DR(47.49±6.59)% in 2.5mg/L HBsAg loading group, CD83(17.88±3.12)%, CD80(45.24± 10.93)% and MHC-DR(47.07±8.52)% in 5mg/L HBsAg loading group and CD83(16.74±2.86)%, CD80(44.59±6.99)% and MHC-DR(48.59±7.42)% in 10mg/L HBsAg loading group, respectively. Compared with the control group, the phenotypic molecules in the experimental groups were all different significantly (P<0.01), but among them, there were no differences (P>0.05). CONCLUSIONS: DCs cultured from PBMCs in the patients with CHB under the conditions of GM-CSF and IL-4 present on the typical dendritic morphology but are immature for expressing low phenotypic molecules. Loaded by different concentrations of HBsAg, the immature DCs can differentiate to mature DCs for expressing increasing phenotypic molecules.
文摘Immune reactions to foreign or self-antigens lead to protective immunity and, sometimes, immune disorders such as allergies and autoimmune diseases. Antigen presenting cells (APC) including epidermal Langerhans cells (LCs) play an important role in the course and outcome of the immune reactions. Epidermal powder immunization (EPI) is a technology that offers a tool to manipulate the LCs and the potential to harness the immune reactions towards prevention and treatment of infectious diseases and immune disorders.
基金supported by the Natural Science Research Foundation of Anhui Province Universities,No.KJ2011A202the National Natural Science Foundation of China,No.81000074
文摘Bone marrow precursor cells were extracted from C57BL/6J mice aged 7-8 weeks, and dendritic cells were purified using anti-CD1 lc (a specific marker for dendritic cells) antibody-coated magnetic beads. Immunofluorescence staining revealed that the expression levels of endomorphin-1 and endomorphin-2 were upregulated in dendritic cells activated by lipopolysaccharide. An enzyme Jmmunoassay showed that lipopolysaccharide and other Toll-like receptor ligands promoted the secretion of endomorphin-1 and endomorphin-2 from activated dendritic cells. [3H]-thymidine incorporation demonstrated that endomorphin-1 and endomorphin-2 both inhibited the proliferation of T lymphocyte induced by activated dendritic cells. Furthermore, this immunosuppressive effect was blocked by CTOP, a specific antagonist of IJ-opioid receptors. Our experimental findings indicate that activated dendritic cells can induce the expression and secretion of endomorphins, and that endomorphins suppress T lymphocyte proliferation through activation of iJ-opioid receptors.
文摘Background and Objectives Autoimmune reaction may play an important role in the pathogenesis and progress in virus myocarditis. Dendritic cells are the initiators of immune reaction to foreign antigens and are considered to be key players in the induction and maintenance of autoimmune reactions. This study was undertaken to investigate the role of DC in mice with virus myocarditis. Methods and Results Fifty Balb/c mice were injected Coxsackie B3 virus to induce myocarditis and ten mice were injected culture liquid as control group. The hearts of virus - infected mice were harvested on day 3, 7, 14, 28 after the injection. All the hearts were sliced to do HE staining, MHC Ⅱ antigen and S - 100 protein immunohistochemical staining. The inflammation response and expression of MHC Ⅱ antigen and S - 100 protein positive stained cells were observed. The MHC Ⅱ antigen positive score were 1.42±0.95, 2.24 ±1. 00, 3. 23± 1. 16, 2. 58 ± 1. 05 respectively in group 3d, 7 d, 14 d, 28 d, which were significant different from control group(0. 50 ±0.75, P <0. 05). The S-100 positive staining cells in control group was 3. 2±1. 0. And the numbers were 6. 7 ± 1. 4 , 16. 4 ± 2. 5 , 21. 2±3. 3 , 13. 4 ± 2. 3 respectively in group 3 d, 7 d, 14 d, 28 d, and there were significant differences compared with the control group ( P < 0. 01) . Conclusions Immune reaction was involved in the pathogenesis in Coxsackie B3 virus - induced myocarditis in mouse, and dendritic cell might play an important role in the immune reaction.
文摘<p style="text-align:justify;"> <span>Following organ transplantation</span><span>,</span><span> the outcome of the encounter between an APC and a T lymphocyte is strongly dependent on the presence of costimulatory and co-inhibitory molecules, the former associated with allograft rejection and the latter with allograft acceptance. We evaluated the expression of PD-L2, GITR, ILT-2/3/5, and ILT-4 on graft-infiltrating cells procured by Fnab from human KTx under different immunosuppressive regimens. Methods: Fnab biopsies were performed on days 7 or 14</span><span> </span><span>-</span><span> </span><span>30 in stable KTx and on the day of acute rejection diagnosis. Cytopreparations were studied by the enzymatic avidin biotin complex staining. Results: Acute rejection group </span><span>showed a significant down-regulated expression of PD-L2, GITR, and ILT-2/3/5 </span><span>as compared to stable group, while for ILT-4 we did not find significant difference. Anti-IL2</span><i><span>α</span></i><span>R and rapamicyn treatment trend to down-regulate ILT-4 expression, although meaningless. A significant</span><span>ly</span><span> positive correlation was observed between PD-L2 and GITR expression in Fnab. The PPV for acute rejection diagnosis for both PD-L2 and GITR w</span><span>as</span><span> clearly above 0.8. Conclusions: Our findings point to an early entrance of cells expressing PD-L2, GITR and ILT-2/3/5 inside human KTx who are going to remain rejection-free. Both PD-L2 and GITR shared a high ability to rule-in and rule-out acute rejection.</span> </p>
基金ACKNOWLEGEMENTS This work was supported by the grants from the following: National Natural Science Foundation of China (no. 30471593, 30872304 and 81072470), Shanghai Commission of Science and Technology (no. 10IC14 08500 and 10ZR1426100), Shanghai Leading Academic Discipline-Surgery (no. $30204- K01), Shanghai Municipal education Commission (no. 150207 and 09YZ102), Shanghai Institute of Immunology (no. 08-A04), Clinical Medicine Technology Development Foundation of Jiangsu University (no. ILY2010091) and Foundation of Shanghai Xuhui Central Hospital (no. 2011XHCH07).
文摘Rheumatoid arthritis is an autoimmune disease that primarily affects the limbs, but the pathogenic mechanism remains unclear. 78 T cells, a T-cell subpopulation, are characterized by multiple biological functions and associated with a variety of diseases. This study investigated the antigen-presenting effects of γδ2 cells and their relationship with rheumatoid arthritis development. We found that Vγ9Vδ2 T cells (the predominant subtype of γδ T cells in peripheral blood) were activated by isopentenyl pyrophosphate to continuously proliferate and differentiate into effector memory cells. The effector memory Vγ9Vδ2 T cells exhibited phenotypic characteristics of specific antigen-presenting cells, including high HLA-DR and CD80/86 expression. These Vγ9Vδ2 T cells could present soluble antigens and synthetic peptides to CD4+ T cells. Vγ9Vδ2 T cells with different phenotypes showed different cytokine secretion patterns. Effector memoryVγ9Vδ2 T cells simultaneously secreted not only interferon (IFN)-γbut also IL-17. The peripheral blood and joint synovial fluid from RA patients contained numerous heterogeneous γδ T cells that were predominantly effector memory Vγ9Vδ2 T cells with the ability to secrete inflammatory factors. We also found that γδ T cells had a similar antigen-presenting capability to B cells. These results suggest that during the development of rheumatoid arthritis, 78 T cells can aggravate immune dysfunction and produce abnormal immune damage by secreting cytokines and inducing inflammatory cells to participate in synergistic inflammatory responses. Furthermore, γδ T cells can behave similarly to B cells to present viral peptides and autoantigen peptides to CD4+ T cells, thus sustaining CD4+ T-cell activation.
基金the National Natural Science Foundation of China(No.30400399,No.30671917)the Natural Science Fund of Jiangsu Province(BK2004404) the Natural Science Fund of the Educational Committee of Jiangsu Province(04KJB320162) in China.
文摘Artificial antigen-presenting cells are expected to stimulate the expansion and acquisition of optimal therapeutic features of T cells before infusion. Here CD32 that binds to a crystallizable fragment of IgG monoclonal antibody was genetically expressed on human K562 leukemia cells to provide a ligand for T-cell receptor. CD86 and 4-1BBL, which are ligands of co-stimulating receptors of CD28 and 4-1BB, respectively, were also expressed on K562 cells. Then we accomplished the artificial antigen-presenting cells by coupling K32/CD86/4-1BBL cell with OKT3 monoclonal antibody against CD3, named K32/CD86/4-1BBL/OKT3 cells. These artificial modified cells had the abilities of inducing CD8^+ T cell activation, promoting CD8^+ T cell proliferation, division, and long-term growth, inhibiting CD8^+ T cell apoptosis, and enhancing CD8^+ T cell secretion of IFN-T and perforin. Furthermore, antigen-specific cytotoxic T lymphocytes could be retained in the culture stimulated with K32/CD86/4-1BBL/OKT3 cells at least within 28 days. This approach was robust, simple, reproducible and economical for expansion and activation of CD8^+ T cells and may have important therapeutic implications for adoptive immunotherapy. Cellular & Molecular Immunology.
基金This study was supported by a grant from the Major Basic Project of China (973) (No. 2005CB522903).
文摘Background The mechanism of chronic immune activation and impairment of HIV-specific immune responses during chronic infection is not fully understood. However, it is known that high immune activation leads to more rapid progression to AIDS. We hypothesize that CD4^+ T cell-mediated viral antigen presentation contributes to this pathologic immune activation in HIV-infected individuals. Methods HIV-specific T cells, responding to noninfectious HIV-1 virions as antigen, were measured by flow cytometric assays. These experimental conditions reflect the in vivo condition where noninfectious HIV-1 represents more than 99% of the antigens. Results CD4^+ T cells purified from HIV-infected individuals were capable of cross presenting exogenous noninfectious HIV-1 virions to HIV-1-specific CD8^+ T cells. Cross presentation required the entry of HIV-1 to CD4^+ T cells and antigen translocation from endoplasmic reticulum to the Golgi complex. Blocking CD4^+ mediated activation of HIV-specific CD8^+ T cells and redirecting the viral antigens to antigen presenting cells improved HIV-specific T cell responses. Contusions One possible cause of chronic immune activation and impairment of HIV-1 specific T cell responses is represented by HIV-1 harboring CD4^+ T cells cross presenting HIV-1 antigen to activate CD8^+ T cells. This new mechanism provides the first evidence that cross presentation of noninfectious HIV-1 virions play a role in the immunopathogenesis of HIV-1 infection.