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@#Abstract: Objective To observe the expression of peripheral blood stimulating molecules CD80 and CD86 in children with severe hand, foot, and mouth disease (HFMD), and to analyze the relationship between them and the therapeutic effects of children. Methods The clinical data of 252 children with severe HFMD treated in Wuhan Hospital of Traditional Chinese Medicine from March 2017 to March 2021 were collected retrospectively. All children were treated with standardized treatment and the therapeutic effects was evaluated. The baseline data and laboratory test results of children were recorded, and the positive rates of CD80 and CD86 cells in peripheral blood were detected by flow cytometry. Logistic regression was used to analyze the relationship between the above indexes and the therapeutic effects of children. The receiver operating curve (ROC) was drawn to evaluate the value of the above indicators in predicting the therapeutic effects of children. Results After standardized treatment, 48 children were ineffective, and 204 children were effective; the levels of serum CD80 [(2.28±0.84)% vs (2.12±0.33 )%] and CD86 [(3.35±0.96)% vs (2.23±0.41)%] in children were significantly lower than those at admission (t=2.851, 16.991; P<0.05). The levels of blood lactic acid, serum C-reactive protein (CRP), matrix metalloproteinase-9 (MMP-9), CD80 and CD86 at admission in the ineffective group were significantly higher than those of the effective group (P<0.05). Logistic regression analysis showed that the overexpression of serum CRP (OR=10.929), MMP-9 (OR=1.926), CD80 (OR=3.943) and CD86 (OR=1.947) at admission might be the risk factors of ineffective (all P<0.05). The results of the goodness of fit test for the model showed that, the goodness of fit was high (χ2=6.245, P=0.620); the model collinearity results showed that the variance inflation factors (VIF) values of each variable were <2, and there was no collinearity among the main indicators; the results of the individual independence test for the model showed that Durbin-Watson statistics (D-W)=0.279 and there was poor mutual independence among main indicators. ROC curve analysis showed that the area under the curve(AUC) of serum CD80 at admission in predicting the therapeutic effects of children was 0.762, the cut-off value was 2.390%, and the specificity, sensitivity and Youden index were 0.598, 0792 and 0.390 respectively; the AUC predicted by CD86 was 0.739, the cut-off value was 3.280%, and the specificity, sensitivity and Youden index were 0.510, 0.896 and 0.406 respectively; the AUC by combined prediction was 0.823, and the specificity, sensitivity and Youden index were 0.696, 0.833 and 0.529 respectively. Conclusions Peripheral blood stimulating molecules CD80 and CD86 are involved in the progression of HFMD. Their overexpression may suggest a high risk of treatment ineffectiveness in children with severe HFMD. Early dynamic monitoring of the expression of serum CD80 and CD86 has a certain predictive value for the therapeutic effect of children.
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@#[摘 要] 免疫检查点（IC）分子CTLA-4和PD-1/PD-L1的发现是肿瘤免疫治疗领域的重大突破。既往对IC受体与配体相互作用的认识通常基于反式作用，即受体和配体分别在不同细胞的细胞膜上表达。越来越多的研究结果揭示，肿瘤微环境中DC的细胞膜上同时表达的PD-L1与CD80之间的顺式作用在抗肿瘤免疫反应过程中具有重要意义。DC细胞膜上的PD-L1与CD80形成顺式异二聚体之后，其中的PD-L1不能再与T细胞膜上的PD-1结合，但其中的CD80却仍可以活化T细胞膜上的CD28。更重要的是，PD-L1:CD80顺式异二聚体对T细胞PD-1和CD28活化能力的这种差异直接关系到肿瘤对于不同的免疫检查点抑制剂（ICI）的反应。
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@#[Abstract] In recent years, investigation on immune checkpoint inhibitors has made exciting progress in anti-tumor therapy. Through continuous exploration, there is a deeper understanding of intermolecular interaction patterns among PD-L1, PD-1, CD80, CTLA-4, etc. In addition to classically acting as a T cell inhibitory receptor, PD-L1 was found to be co-expressed with PD-1 or CD80 on the same cell and play a positive immunoregulatory function through cis-interaction, significantly affecting the interaction network between tumor cells and immune cells and the efficacy of immunotherapy, and bringing new changes to the understanding of the mechanisms of cancer immunotherapy. This review provides an in-depth analysis of the cis-PD-L1/PD-1 and cis-PD-L1/CD80 pathways and their interactions with a complex network of CTLA-4 and CD28 molecules, finally outlines the effects of blocking this cis-interaction pathway on T cell signaling, cytotoxic function, and the efficacy of anti-tumor immunotherapy.
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Minimal change nephrotic syndrome (MCNS) is the most common nephrotic syndrome among children.Although the details of pathogenesis remain unknown, it is widely considered that upregulated expression of T lymphocyte cell cytokines contributes to the initiation of MCNS.Moreover, studies had revealed that altered number and function disorder of B lymphocyte cells could change the functions of antigen presentation, participating in the onset of MCNS by affecting the function of T lymphocyte cells.Recently, CD80 has emerged as a popular research topic which exerts its effects via the change of podocytes morphology, thereby affecting the glomerular permeability.However, neither immune disorder nor podocyte dysfunction is poorly demonstrated to be associated with the pathogenesis of MCNS, the hypothesis such as "a 'two hit disorder" and "γδT cells exacerbate podocyte injury via the CD28/B7-1-phosphor-SRC kinase pathway" are raised.In the current review, we summarized the related investigations to help us to understand the mechanisms and pathogenesis of MCNS.
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Minimal change nephrotic syndrome (MCNS) is the most common nephrotic syndrome among children.Although the details of pathogenesis remain unknown,it is widely considered that upregulated expression of T lymphocyte cell cytokines contributes to the initiation of MCNS.Moreover,studies had revealed that altered number and function disorder of B lymphocyte cells could change the functions of antigen presentation,participating in the onset of MCNS by affecting the function of T lymphocyte cells.Recently,CD80 has emerged as a popular research topic which exerts its effects via the change of podocytes morphology,thereby affecting the glomerular permeability.However,neither immune disorder nor podocyte dysfunction is poorly demonstrated to be associated with the pathogenesis of MCNS,the hypothesis such as "a two hit disorder" and "γδT cells exacerbate podocyte injury via the CD28/B7-1-phosphor-SRC kinase pathway" are raised.In the current review,we summarized the related investigations to help us to understand the mechanisms and pathogenesis of MCNS.
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Background:Ant venoms express surface molecules that participate in antigen presentation involving pro- and anti-inflammatory cytokines. This work aims to investigate the expression of MHC-II, CD80 and CD86 on the polymorphonuclear cells (PMNs) in rats injected with samsum ant venom (SAV).Methods:Rats were divided into three groups - control, SAV-treated (intraperitoneal route, 600 μg/kg), and SAV-treated (subcutaneous route, 600 μg/kg). After five doses, animals were euthanized and samples collected for analysis.Results:The subcutaneous SAV-trated rats presented decreased levels of glutathione with increased cholesterol and triglyceride levels. Intraperitoneal SAV-treated animals displayed significantly reduced concentrations of both IFN-γ and IL-17 in comparison with the control group. However, intraperitoneal and subcutaneous SAV-treated rats were able to upregulate the expressions of MHC-II, CD80 and CD86 on PMNs in comparison with the control respectively. The histological examination showed severe lymphocyte depletion in the splenic white pulp of the intraperitoneal SAV-injected rats.Conclusion:Stimulation of PMNs by SAV leads to upregulation of MHC-II, CD 80, and CD 86, which plays critical roles in antigen presentation and consequently proliferation of T-cells. Subcutaneous route was more efficient than intraperitoneal by elevating MHC-II, CD80 and CD86 expression, disturbing oxidative stability and increasing lipogram concentration.
Subject(s)
Animals , Major Histocompatibility Complex , Oxidation-Reduction , Spider Venoms/analysis , Spider Venoms/immunologyABSTRACT
CD80, CD86 and their receptors CD28 and CTLA-4 provide the necessary costimulatory signals for T cell. Virus infection may inhibit the expression of CD80 or CD86 to impair the function of specific T lymphocytes, thus avoid immune surveillance; it can also lead to the disorder of the expression of CD80 or CD86, inducing dysfunction of immune cells in the body, thus causing continuous infection and inflammation. Therefore, costimulation pathway CD80/CD86: CD28/CTLA-4 has great significance for the body to maintain a normal immune response, as well as the clearance of the virus and the recovery of the body. This article summarizes the studies on CD80, CD86 and their receptors in viral infection in recent years, and provides theoretical ideas and references for the control of viral infection.
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Objective To study the therapeutic effect of anti-CD80 bivalent antibody on mouse lu-pus nephritis and to explore the possible molecular mechanism. Methods A mouse model of lupus nephritis was established through intraperitoneal injection of 0. 5 ml of pristine in female C57BL/6J mice. Appearance of urinary protein and significantly increased levels of peripheral antinuclear antibody ( ANA) and anti-doub-le-stranded DNA ( anti-dsDNA) antibody in the fourth month after injection indicated that the mouse model was established successfully. Then the mice were divided into two groups including anti-CD80 bivalent anti-body intervention group (injected with 200μg of anti-CD80 bivalent antibody at day 1, 3, 5, 8 and 15, fol-lowed by three times of injection with an interval of one month) and model group ( injected with the same protein using the same strategy). A normal control group was set up accordingly. Albustix test paper was used to monitor the dynamic changes in mouse urinary protein. Flow cytometry was used to analyze the acti-vation of immune-related cells in spleen. Levels of autoantibodies ( ANA and anti-dsDNA) and levels of IFN-γ and IL-4 in serum were detected by indirect immunofluorescence assay. Renal tissue samples were an-alyzed with hematoxylin and eosin ( HE) staining and immunocomplex ( IC) assay. Results Urinary pro-tein level of the anti-CD80 bivalent antibody intervention group was significantly lower than that of the model group (P<0. 05). Activated macrophages, dendritic cells, neutrophils and B cells in spleen tissues of the anti-CD80 bivalent antibody intervention group were significantly less than those of the model group ( P<0. 05), and the numbers of CD4+ and CD154+ T cells were significantly less than those of the model group (P<0. 05). Positive rates and titers of ANA and dsDNA in serum samples of the intervention group were lower than those of the model group (P<0. 05). Levels of IFN-γand IL-4 in serum samples of the interven-tion group were decreased as compared with those of the model group (P<0. 05). HE staining and immuno-fluorescence assay showed that glomerular inflammatory injury and necrosis were alleviated and kidney im-mune complex deposition was reduced after anti-CD80 bivalent antibody intervention. Conclusion Anti-CD80 bivalent antibody specifically binds to the CD80 molecule on antigen presenting cell surface, blocks the CD80/CD28 co-stimulatory signaling pathway and down-regulates the body′s immune response, which al-leviates and reverses the lupus-like nephritis-induced pathological damages in mice.
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Objective To study the therapeutic effect of anti-CD80 bivalent antibody on mouse lu-pus nephritis and to explore the possible molecular mechanism. Methods A mouse model of lupus nephritis was established through intraperitoneal injection of 0. 5 ml of pristine in female C57BL/6J mice. Appearance of urinary protein and significantly increased levels of peripheral antinuclear antibody ( ANA) and anti-doub-le-stranded DNA ( anti-dsDNA) antibody in the fourth month after injection indicated that the mouse model was established successfully. Then the mice were divided into two groups including anti-CD80 bivalent anti-body intervention group (injected with 200μg of anti-CD80 bivalent antibody at day 1, 3, 5, 8 and 15, fol-lowed by three times of injection with an interval of one month) and model group ( injected with the same protein using the same strategy). A normal control group was set up accordingly. Albustix test paper was used to monitor the dynamic changes in mouse urinary protein. Flow cytometry was used to analyze the acti-vation of immune-related cells in spleen. Levels of autoantibodies ( ANA and anti-dsDNA) and levels of IFN-γ and IL-4 in serum were detected by indirect immunofluorescence assay. Renal tissue samples were an-alyzed with hematoxylin and eosin ( HE) staining and immunocomplex ( IC) assay. Results Urinary pro-tein level of the anti-CD80 bivalent antibody intervention group was significantly lower than that of the model group (P<0. 05). Activated macrophages, dendritic cells, neutrophils and B cells in spleen tissues of the anti-CD80 bivalent antibody intervention group were significantly less than those of the model group ( P<0. 05), and the numbers of CD4+ and CD154+ T cells were significantly less than those of the model group (P<0. 05). Positive rates and titers of ANA and dsDNA in serum samples of the intervention group were lower than those of the model group (P<0. 05). Levels of IFN-γand IL-4 in serum samples of the interven-tion group were decreased as compared with those of the model group (P<0. 05). HE staining and immuno-fluorescence assay showed that glomerular inflammatory injury and necrosis were alleviated and kidney im-mune complex deposition was reduced after anti-CD80 bivalent antibody intervention. Conclusion Anti-CD80 bivalent antibody specifically binds to the CD80 molecule on antigen presenting cell surface, blocks the CD80/CD28 co-stimulatory signaling pathway and down-regulates the body′s immune response, which al-leviates and reverses the lupus-like nephritis-induced pathological damages in mice.
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Adiponectin is a multifunctional adipokine that has several oligomeric forms in the blood stream, which broadly regulates innate and acquired immunity. Therefore, in this study, we aimed to observe the differentiation of T helper (Th) cells and expression of costimulatory signaling molecules affected by adiponectin. The mRNA and protein expression levels of adiponectin and its receptors in oxidized low density lipoprotein cholesterol-treated endothelial cells were assayed by real time PCR and immunofluorescence. The endothelial cells were then treated with adiponectin with or without adipoR1 or adipoR2 siRNA and co-cultured with T lymphocytes. The distribution of Th1, Th2 and Th17 subsets were assayed by flow cytometry. The effects of adiponectin on costimulatory signaling molecules HLA-DR, CD80, CD86 and CD 40 was also assayed by flow cytometry. The results showed that endothelial cells expressed adiponectin and its receptor adipoR1 and adipoR2, but not T-cadherin. Adiponectin suppressed Th1 and Th17 differentiation through adipoR1 receptor, contributed to the inhibition of CD80 and CD40, and inhibited differentiation of Th1 and Th17 by inhibiting antigen presenting action.
Subject(s)
Humans , Infant, Newborn , Adult , Adiponectin/metabolism , B7-1 Antigen/metabolism , CD40 Antigens/metabolism , T-Lymphocytes, Helper-Inducer/drug effects , Adiponectin/genetics , Adiponectin/pharmacology , Cell Differentiation , Cells, Cultured , Endothelial Cells/drug effects , Endothelial Cells/metabolism , HLA-DR Antigens/metabolism , Human Umbilical Vein Endothelial Cells/cytology , Lipoproteins, LDL/pharmacology , Receptors, Adiponectin/drug effects , Receptors, Adiponectin/metabolism , T-Lymphocytes, Helper-Inducer/cytology , T-Lymphocytes, Helper-Inducer/metabolismABSTRACT
Objective To observe the regularity of expression changes in CD80 in peripheral blood, lung and splenic dendritic cells (DCs) in mice with acute lung injury (ALI) induced by lipopolysaccharide (LPS) and its correlation with lung inflammation. Methods Twelve C57BL/6 mice were randomly divided into two groups, namely control group and ALI group, with 6 mice in each group. LPS (2 mg/kg) was intra-tracheal instilled in mice to reproduce ALI model, while the control mice received intra-tracheal administration of phosphate buffer saline (PBS) instead. The mice were sacrificed 6 hours after model reproduction, lung tissues were collected, and lung coefficient was calculated (lung wet weight/body weight ×100%). The pathological changes were examined under optical microscope after hematoxylin and eosin (HE) straining, the severity of lung injury was evaluated by the Smith score. Interleukin-6 (IL-6) level was determined by enzyme-linked immunosorbent assay (ELISA). After single-cell suspensions were isolated from the lung and spleen, the level of CD80 on DC in peripheral blood, lung and spleen was assessed by flow cytometry (FCM). The correlation between CD80 positive DC number and the severity of lung injury was analyzed by Spearman correlation method. Results Compared with control group, LPS-induced ALI resulted in a significant increase in lung coefficient [(0.67±0.04)% vs. (0.52±0.02)%, P 0.05]. In contrast, there were a low but significantly higher percentage of CD80 positive DCs in the lung and spleen in ALI group than that in control group [Lung: (9.6±2.5)% vs. (3.6±1.2)%, spleen: (25.2±4.7)% vs. (9.0±3.6)%, both P < 0.05]. It was shown by the Spearman correlation analyses that respiratory CD80 positive DCs number was significantly positively correlated with IL-6 level in the lung (r = 0.761, P = 0.042) and the Smith score (r = 0.752, P = 0.047). Conclusions There is a significantly higher percentage of CD80 positive DCs in the lung and spleen in ALI mice, and a significantly positively correlation between respiratory CD80 positive DCs number and IL-6 level in the lung or the Smith score, which suggests elevated expression of CD80 on dendritic cells seems to play an important role in the pathogenesis of acute lung injury.
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@#Autophagosomes derived from tumor cells have been proved to induce potent T cell response both in mouse and human. In human in vitro study, dendritic cells(DC)loaded with cytomegalovirus(CMV)pp65 antigen-containing DRibble were capable to efficiently re-stimulate pp65-specific T-cell recall responses from freshly isolated or frozen humanperipheral blood mononuclear cell(PBMC). This study developed more robust assays using in vitro expanded antigen-specific T cells that contained a much higher percentage of antigen-specific T cells. DC cross-presentation efficiency of OX40 and CD80 modified pp65-DRibble was detected by intracellular IFN-γ staining. Compared with Ctrl/pp65 DRibble, the percentage of IFN-γ+ in total CD8+ T cells andCD4+ T cells was improvedwith OX40/pp65 DRibbleand CD80/pp65 DRibble stimulation. In addition, vaccine induced IL-12indendritic cells, whichpolarizes Th cells toward the IFN-γ high Th1 phenotype, evaluated by ELISA inco-culture supernatantwas dramatically higher in OX40/pp65 DRibble and CD80/pp65 DRibblegroups than in Ctrl/pp65 DRibble group. These results have implications for the immuneactivity of OX40 and CD80 modified DRibble and choice for prospective clinical use ofDRibble-based cancer immunotherapy.
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Idiopathic nephrotic syndrome (INS) in children is characterized by massive proteinuria and hypoalbuminemia. Minimal change nephrotic syndrome (MCNS) is the most common form of INS in children. The pathogenesis of MCNS still remains unclear, however, several hypotheses have been recently proposed. For several decades, MCNS has been considered a T-cell disorder, which causes the impairment of the glomerular filtration barrier with the release of different circulating factors. Increased levels of several cytokines are also suggested. Recently, a "two-hit" theory was proposed that included the induction of CD80 (B7-1) and regulatory T-cell (Treg) dysfunction, with or without impaired autoregulatory functions of the podocyte. In contrast to the well-established involvement of T cells, the role of B cells has not been clearly identified. However, B-cell biology has recently gained more attention, because rituximab (a monoclonal antibody directed against CD20-bearing cells) demonstrated a very good therapeutic response in the treatment of childhood and adult MCNS. Here, we discuss recent insights into the pathogenesis of MCNS in children.
Subject(s)
Adult , Child , Humans , B-Lymphocytes , Biology , Cytokines , Glomerular Filtration Barrier , Hypoalbuminemia , Nephrosis, Lipoid , Nephrotic Syndrome , Podocytes , Proteinuria , Rituximab , T-LymphocytesABSTRACT
Objective To investigate the expression of Toll-like receptor 4 (TLR4) and CD80 in unexplained recurrent spontaneous abortion and their relationship,discuss its possible roles in guiding eugenics,and provide a new idea for clinical diagnosis and prevention.Methods The study group were 60 cases with unexplained recurrent spontaneous abortion patients.The control group included 30 cases of normal early pregnancy without previous history of adverse pregnancy.The expressions of TLR4 and CD80 were detected with immunohistochemistry in the peripheral blood,chorion,and decidua from each case.Results TLR4 had higher expression in the peripheral blood,the chorion and decidua from the recurrent spontaneous abortion women than that from normal pregnancy women (P ＜ 0.05).Levels of CD80 were significantly higher in recurrent spontaneous abortion group than in normal pregnancy group (P ＜ 0.05).There was a positive correlation between TLR4 and CD80 (r =0.982,0.986,and 0.776,P ＜0.01).Conclusions The study shows that TLR4 and CD80 were expressed in peripheral blood lymphocytes and villi and decidua of early pregnancy (normal pregnancy or abnormal pregnancy).Higher expressions of TLR4 and CD80 might play an important role in the occurrence of recurrent spontaneous abortion.
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For children suffering from primary nephrotic syndrome(PNS), podocyte is a crucial part of glomerular filtration barrier, whose injury usually causes proteinuria.The structural and functional integrity of podocyte cytoskeleton is the prerequisite of its normal physiological function.Recent studies demonstrated that under a certain pathological condition, B7-1, expressed in podocyte, can inhibit the activation of β1 integrin by competitively binding to the target site on the β1 integration, which may change the morphology and function of podocyte, consequently induced proteinuria.Other studies also have showed that abatacept, which selectively inhibit the cross-talk between B7-1 and β1-integrin,can reduce proteinuria in patients with B7-1-positive glomerular disease.These studies suggested that B7-1 may be a potential diagnostic biomarker and therapeutic target in proteinuria in PNS.This review summarizes the role of B7-1 expressed in podocyte in the pathogenesis of proteinuria and the possibility of clinical application in the future.
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Objective:To explore the influence of IL-18 on the expression of MHCⅠ,MHCⅡ,CD80,CD86 on the surface of 9L cells,to identify the effect of IL-18 on the immunogenicity and the efficiency of tumor antigen presentation of 9L.Methods:Retroviruses were used to transduce the mIL-18 gene into rat glioma cells and the cell clones (9L/IL-18) which steadily expressing mIL-18 gene were obtained ,and got the control cells of 9L/LXSN by the same method.The expression of MHCⅠ,MHCⅡ,CD80,CD86 on the cell surface were assessed by flow cytometry.The cell suspension of 9L/IL-18,9L/LXSN and 9L cells were inoculated into the brain of F344 rat to establish the animal models by the stereotactic technique ,got the tumor tissues to analyze the expression of MHCⅠ, MHCⅡ,CD80 and CD86 on the surface of tumor cells after 14 days.Results:The expression of MHCⅠ,MHCⅡ,CD80 and CD86 on the surface of 9L/IL-18 were (10.9±1.44)%,(0.61±0.14)%,(1.01±0.14)%,(0.57±0.11)% ; had no significant differences with the others in vitro (P>0.05);while the expression of MHCⅠ,CD80 and CD86 on the surface of 9L/IL-18 were(67.51± 1.40)%,(12.51±1.57)%,(6.95±0.56)%which were higher than 9L/LXSN and 9L cells (P0.05) in vivo.Conclusion: IL-18 did not affect the immunogenicity of 9L in vitro,but improve the immunogenicity and tumor antigen presentation in vivo.
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One of the mechanisms by which adjuvants are believed to promote T-cell activation and prevent induction of oral tolerance is by up-regulating the expression of co-stimulatory molecules on antigen presenting cells. Mice treated orally with palmitoyl-ovalbumin conjugates become immunized, while those treated with native ovalbumin (Ova) become tolerant. Cells from the peritoneal cavity of B6D2F1 mice were cultured in the presence of 0.01, or 0.1 mg/100ml of either Ova, or palmitoyl-Ova and tested for the presence of cell markers. PE-conjugated anti-mouse CD80, CD86, and CD11b antibodies as well as biotin-PE were used to stain the antigen-activated peritoneal cells. A significant increase in the expression of CD86 and CD80 was observed following in vitro stimulation with palmitoyl-Ova; additionally, both Ova and palmitoyl-Ova induced the basal expression of CD11b. These findings could be related with the strong T-cell proliferative response induced by palmitoyl-Ova.
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Leprosy is a spectral disease exhibiting two polar sides, namely, lepromatous leprosy (LL) characterised by impaired T-cell responses and tuberculoid leprosy in which T-cell responses are strong. Proper T-cell activation requires signalling through costimulatory molecules expressed by antigen presenting cells and their ligands on T-cells. We studied the influence of costimulatory molecules on the immune responses of subjects along the leprosy spectrum. The expression of the costimulatory molecules was evaluated in in vitro-stimulated peripheral blood mononuclear cells of lepromatous and tuberculoid patients and healthy exposed individuals (contacts). We show that LL patients have defective monocyte CD86 expression, which likely contributes to the impairment of the antigen presentation process and to patients anergy. Accordingly, CD86 but not CD80 blockade inhibited the lymphoproliferative response to Mycobacterium leprae. Consistent with the LL anergy, there was reduced expression of the positive signalling costimulatory molecules CD28 and CD86 on the T-cells in these patients. In contrast, tuberculoid leprosy patients displayed increased expression of the negative signalling molecules CD152 and programmed death-1 (PD-1), which represents a probable means of modulating an exacerbated immune response and avoiding immunopathology. Notably, the contacts exhibited proper CD86 and CD28 expression but not exacerbated CD152 or PD-1 expression, suggesting that they tend to develop a balanced immunity without requiring immunosuppressive costimulatory signalling.
Subject(s)
Adult , Female , Humans , Male , /immunology , /immunology , /immunology , Leprosy/microbiology , Mycobacterium leprae/immunology , Programmed Cell Death 1 Receptor/immunology , T-Lymphocytes/immunology , /metabolism , /metabolism , /metabolism , Case-Control Studies , Host-Parasite Interactions , Leprosy/immunology , Mycobacterium leprae/physiology , Programmed Cell Death 1 Receptor/metabolismABSTRACT
Vitamin C is an essential water-soluble nutrient which primarily exerts its effect on host defense mechanisms and immune homeostasis, but the mechanism related to immune-potentiation is poorly understood. Since dendritic cells (DCs) are known as a potent antigen presenting cell (APC) that could enhance the antigen specific immune responses, we investigate the effects of vitamin C on activation of DCs and its related mechanism by using dendritic cell lines, DC-1. First, we found that there was no damage on DC-1 by 2.5 mM of vitamin C. In the presence of vitamin C, the expression of CD80, CD86, and MHC molecules was increased, but it was decreased by the pre-treatment of SB203580, p38 MAPK-specific inhibitor. We confirmed the phosphorylation of p38 MAPK was increased by the treatment of vitamin C. Taken together, these results suggest that vitamin C could enhance the activity of dendritic cells via the up-regulation of the expression of CD80, CD86, and MHC molecules and the activation of p38 MAPK is related to this process.
Subject(s)
Ascorbic Acid , Defense Mechanisms , Dendritic Cells , Homeostasis , Imidazoles , p38 Mitogen-Activated Protein Kinases , Phosphorylation , Pyridines , Up-Regulation , VitaminsABSTRACT
BACKGROUND: Epstein Barr virus (EBV) infected B cells are transformed into lymphoblastoid cell lines. Some researchers suggested some a few similarities between this process and carcinogenesis. We observed the expression of CD80 and CD86, co-stimulatory molecules on EBV-transformed B cells and changes of CD54 expression after stimulation of CD80 and CD86. METHODS: CD80 and CD86 were stimulated using anti-CD80 and anti-CD86 monoclonal antibodies. To assess apoptosis and surface protein expression, flow cytometric analysis was performed. Intracellular signal molecules were evaluated by RT-PCR and immunoblot. Morphology and localization of proteins were examined using inverted or confocal microscope. RESULTS: Cross-linking of CD80 and CD86 induced apoptosis and interfered with proliferation of EBV-transformed B cells, and dispersion of clumped cells. We also examined that their stimulation induced ROS accumulation and reduced CD54 expression. Interestingly, we observed that CD80 and CD86 diminished the expression of CD54 in different methods. Both CD80 and CD86 down-regulated activation of focal adhesion kinase. CD80 stimulus inhibited CD54 expression through mainly RhoA inactivation, while CD86 down-regulated Ras and JNK phosphorylation. CONCLUSION: These results suggest that co-stimulatory CD80 and CD86 molecules, expressed EBV-transformed B cells, may play a role in apoptosis and cell adhesion.