Application study on adoptive transfusion of tolerogenic dendritic cells in promoting immune tolerance of liver transplantation in rat models / 器官移植

Objective To investigate the role of tolerogenic dendritic cell (tolDC) in inducing immune tolerance in liver transplantation. Methods Liver transplantation rat models of spontaneous tolerance [Brown Norway (BN)→Lewis, tolerance group, n=6] and acute rejection (AR) (Lewis→BN) were established. In AR rat models, tolDC transfusion was performed in the study group (tolDC group, n=6) and no intervention was given in the control group (AR group, n=6). The survival time of rats in each group was observed. The transplant liver tissues of rats were prepared for pathological examination in each group. The expression of myeloid dendritic cell (mDC) and plasmacytoid dendritic cell (pDC) in rat peripheral blood, transplant liver, spleen and lymph nodes in each group was detected by flow cytometry. The expression levels of serum interleukin (IL)-10 and interferon (IFN)-γ in each group were measured by enzyme-linked immune absorbent assay. Results Pathological manifestations of rats in the AR group mainly included inflammatory cell infiltration and tissue structural disorder in transplant liver, and the survival time was 7-14 d. In the tolDC and tolerance groups, the transplant liver tissues were almost normal, and the longest survival time exceeded 100 d. Compared with the AR group, the expression levels of CD11+mDC in peripheral blood, transplant liver, spleen and lymph nodes of rats were significantly down-regulated in the tolerance and tolDC groups (all P < 0.05), and those of CD86 and major histocompatibility complex (MHC)Ⅱon the surface of CD11+mDC were also significantly down-regulated (all P < 0.05). Compared with the AR group, the expression levels of pDC in peripheral blood, transplant liver, spleen and lymph nodes of rats were significantly up-regulated in the tolerance and tolDC groups (all P < 0.05), whereas those of MHCⅡon the surface of pDC were all significantly down-regulated (all P < 0.05). Compared with the AR group, the expression levels of serum IL-10 were significantly up-regulated, and IFN-γ were significantly down-regulated in the tolerance and tolDC groups (all P < 0.05). Conclusions As tolDC subsets, mDC and pDC play a positive role in regulating the incidence of graft immune tolerance in rats after liver transplantation.

Relationship between the expression of peripheral blood stimulating molecules CD80, CD86 and the therapeutic effects of children with severe hand, foot, and mouth dise / 中国热带医学

@#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.

Samsum ant venom modulates the immune response and redox status at the acute toxic dose in vivo

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.

Role of CD80, CD86 and their receptors in the immune response in virus infection / 中华实验和临床病毒学杂志

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.

Effects of an anti-CD86 chimeric antibody (ch1D1) on autoreactive B lymphocytes isolated from pa-tients with SLE / 中华微生物学和免疫学杂志

Objective To investigate the effects of ch1D1, an anti-CD86 chimeric antibody, on autoreactive B lymphocytes isolated from patients with systemic lupus erythematosus ( SLE) . Methods Flow cytometry analysis was performed to measure the expression of CD86 on the surface of B cells isolated from patients with SLE and to analyze the effects of ch1D1 on the activation of CD4+T cells. The method of magnetic bead sorting was used to separate B cells, NK cells and CD4+T cells from PBMC collected from healthy subjects and patients with SLE for subsequent experiments. Antibody-dependent cell-mediated cyto-toxicity (ADCC) and complement-dependent cytotoxicity (CDC) that were mediated by ch1D1 were meas-ured with LDH release assay. Effects of ch1D1 on the secretion of auto-antibodies and the proliferation of CD 4+ T were detected by ELISA and 3 H -thymidine ( 3 H-TdR) incorporation assay, respectively. Results The levels of CD80 (68. 08±14. 28 vs 46. 10±12. 14, n=24, P<0. 000 1) and CD86 (44. 72±14. 90 vs 13. 99±10. 74, n=24, P<0. 000 1) expressed on the surface of B cells isolated from patients with SLE were significantly higher than those from the healthy subjects, suggesting the abnormal activation of B cells. Com-pared with the negative control group and the murine monoclonal antibody 1D1, ch1D1 was more effective in mediating the ADCC and CDC responses (P=0. 017 2, P=0. 038 8). Activated T cells significantly en-hanced the secretion of auto-antibodies by B cells isolated from patients with SLE. Compared with the nega-tive control group, the enhanced secretion of auto-antibodies was significantly inhibited by treatment with ch1D1 (P=0. 001 9). Moreover, ch1D1 significantly inhibited the proliferation and activation of CD4+T cells induced in patients with SLE (P=0. 002 4, P=0. 049 5). Conclusion ch1D1, the anti-CD86 chim-eric antibody, could effectively mediate the ADCC and CDC responses against autoreactive B cells isolated from patients with SLE, inhibit the secretion of auto-antibodies and suppress the proliferation and activation of auto-reactive CD4+T cells. It might be a potential immunotherapy agent for the treatment of SLE.

Significance of the expression of Toll-like receptor and costimulatory molecule of dendritic cells in the peripheral blood in children with Henoch-Sch(o)nlein purpura / 中华实用儿科临床杂志

Objective To observe the expression of Toll-like receptor(TLR) on peripheral blood dendritic cells(DC) in children with Henoch-Schtinlein purpura(HSP),and to investigate the pathogenesis of the abnormal expression of TLR in children with HSP.Methods Twenty hospitalized children with HSP in the Affiliated Hospital of Qingdao University Medical College from Dec.2011 to Jul.2012 were enrolled in the study(HSP group).Twenty agemetched healthy children were selected as a healthy control group.Peripheral venous blood was sampled under aseptic condition,peripheral blood mononuclear cells (PBMC) were isolated from density gradient centrifugation,and DC were generated by recombinat human granulocyte-macrophage colony-stimulating factor(GM-CSF),interleukin-4(IL-4) and tumor necrosis factor-α(TNF-α) in vitro.Expressions of CD83,CD86 and TLR2,TLR3,TLR4 in peripheral blood DC were examined by fluorescent activated cell sorter (FACS).Results 1.No significant distinction was found in the expression of the C Ds3 on peripheral blood DC between HSP group and healthy control group(t =0.80,P ＞ 0.05) ;in HSP group had remarkably increased expression of the CD86 on peripheral blood DC than that of the healthy control group (t =9.56,P ＜ 0.01).2.Expression rates of TLR2,TLR3,TLR4 on peripheral blood DC in the HSP group were higher than those in the healthy control group(t =1 1.79,13.29,9.45,all P ＜ 0.01).3.Expression rates of TLR2,TLR3 and TLR4 in HSP group had positive correlation with expression rates of CD86 (r =0.84,P ＜ 0.01 ; r =0.53,P ＜ 0.05 ; r =0.66,P ＜ 0.05).Conclusions Expressions of TLR2,TLR3 and TLR4 on peripheral blood DC significantly increased and were positively correlated with expression of CD86.This implies that TLR and co-stimulatory molecules might participate in the pathogenesis of HSP by mediating signal transduction,leading to abnormity of cytokines,then inducing Th1/Th2 immune imbalance by showing the advantage of Th2 function.

Effect of IL-18 on expression of molecule on surface of 9 L in vitro and in vivo / 中国免疫学杂志

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.

The Interaction Between Allelic Variants of CD86 and CD40LG: A Common Risk Factor of Allergic Asthma and Rheumatoid Arthritis

PURPOSE: Allergic asthma (AA) and rheumatoid arthritis (RA) are immune tolerance-related diseases, and immune tolerance is known to be influenced by costimulatory molecules. In this study, we sought to identify common genetic susceptibility in AA and RA. METHODS: Two hundred cases of AA, 184 cases of RA, and 182 healthy controls were recruited at the Seoul National University Hospital, Seoul, Korea. Eight single nucleotide polymorphisms (SNPs) in five genes coding costimulatory molecules, namely, -318C>T, +49A>G, and 6230G>A in CTLA4, IVS3+17T>C in CD28, -3479T>G and I179V in CD86, -1C>T in CD40, and -3458A>G in CD40LG were scored, and genetic interactions were evaluated by multifactor dimensionality reduction (MDR) analysis. RESULTS: MDR analysis revealed a significant gene-gene interaction between -3479T>G CD86 and -3458A>G CD40LG for AA. Subjects with the T/T genotype of -3479T>G CD86 and the A/A genotype of -3458A>G CD40LG were found to be significantly more likely to develop AA than those with the T/T genotype of -3479T>G CD86 and A/- genotype of -3458A>G CD40LG (adjusted OR, 6.09; 95% CI, 2.89-12.98; logistic regression analysis controlled by age). Similarly those subjects showed a significant risk of developing RA (adjusted OR, 39.35; 95% CI, 15.01-107.00, logistic regression analysis controlled by age). CONCLUSIONS: Our findings suggest that a genetic interaction between CD86 and CD40LG favors the development of both AA and RA.

Expression of costimulatory molecules in antigen-activated peritoneal macrophages treated with either ovalbumin or palmitoyl-ova conjugates

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.

Perfil de células natural killer e dendríticas em casos de soroconversão espontânea e infecção crônica pelo vírus da Hepatite C / Profile of natural killer and dendritic cells in cases of spontaneous clearance and chronic infection with Hepatitis C virus

INTRODUÇÃO: O fato do vírus da Hepatite C (HCV) estabelecer uma infecção crônica persistente, na maioria dos casos, mesmo sendo reconhecido e alvejado pelos sistemas imune inato e adaptativo sugere que o mesmo tenha desenvolvido estratégias eficazes para driblar a ação desses sistemas. O HCV interfere na fase inicial de ativação da resposta imune adaptativa alterando a função das células dendríticas (DCs), o que provavelmente leva a uma ativação deficiente das células natural killer (NKs) e de linfócitos T. Portanto, a realização de estudos sobre DCs e NKs na infecção pelo HCV se torna de fundamental importância para a compreensão da patogênese e persistência desta infecção. MÉTODOS: Foram selecionados indivíduos com resolução espontânea da infecção pelo HCV, indivíduos com infecção crônica e indivíduos saudáveis. A técnica de citometria de fluxo foi utilizada para a determinação da frequência e do fenótipo de células dendríticas e NKs nesses indivíduos. Além disso, foi avaliada a atividade citotóxica das células NKs sob estímulo de IL-12 e IL-18, e também da linhagem K-562. RESULTADOS: A frequência de DC mielóides (mDC) expressando CD86, nos indivíduos crônicos, foi elevada e uma correlação positiva com a carga viral foi observada. Na análise do ensaio funcional foi observado que as populações de células NKs CD7+ CD57+ apresentaram maior expressão da molécula CD107a e baixa produção de IFNy nos indivíduos com infecção crônica. A constante exposição das células imunes ao IFN-alfa, induzido durante a infecção pelo HCV, resulta na polarização do fenótipo citotóxico, caracterizado por células NK ativadas com elevado poder de degranulação, mas com deficiente produção de IFN-y. CONCLUSÕES: As frequências das células DCs e NKs eram semelhantes em todos os indivíduos. A expressão da molécula CD86 na superfície das mDCs pode ter sido induzida pela presença do HCV, uma vez que foi observada correlação positiva com a carga viral...

INTRODUCTION: Hepatitis C virus (HCV) develops a chronic persistent infection in most of the cases, even being recognized and targeted by the innate and adaptive immune systems, suggests that the virus have developed effective strategies to circumvent the action of these systems. HCV interferes in the initial activation of the adaptive immune response by altering the function of dendritic cells (DCs), which probably leads to a deficient activation of natural killer cells (NK) and T lymphocytes. Therefore, studies of DCs and NK in HCV infection are very important for understanding the pathogenesis and the persistence of this infection. METHODS: We selected subjects with spontaneous resolution of HCV infection, with chronic infection and healthy subjects. Flow Cytometry was used to determine the frequency and phenotype of dendritic cells and NK cells of these individuals. In addition, we evaluated the NK cell cytotoxic activity in response to stimulation of IL-12 and IL-18 and in co-cultivation with the cell line K-562. RESULTS: In individuals with chronic infection, the frequency of myeloid (m) DC cells expressing CD86 was elevated and a positive correlation between these cells and viral load was observed. It was observed in chronic infected individuals that NK cells co-expressing CD7 and CD57 showed higher expression of CD107a and low production of IFN gamma. The constant exposure of immune cells to IFN-alfa induced during HCV infection results in the polarization of cytotoxic phenotype characterized by activated NK cells with high power degranulation, but with impaired production of IFN-y. CONCLUSIONS: The frequency of DCs and NK cells were similar in all individuals. The expression of CD86 molecule on the surface of mDCs may have been induced by the presence of HCV, since a positive correlation was observed with viral load. Cytotoxic NK cells, highly differentiated and unable to produce IFN-y, were the most frequent in chronic HCV infection...

Differential expression of the costimulatory molecules CD86, CD28, CD152 and PD-1 correlates with the host-parasite outcome in leprosy

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.

Vitamin C Up-regulates Expression of CD80, CD86 and MHC Class II on Dendritic Cell Line, DC-1 Via the Activation of p38 MAPK

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.

The expression of costimulatory molecules CD86 in acute myelogenous leukemic cells and clinical implication / 中国医师杂志

Objective To investigate costimulatory molecules CD80 and CD86 expression in acute myelogenous leukemic cells and clinical implication.MethodsThe expression of CD80 and CD86 in the patients with acute myelogenous leukemia and HL-60 cells,U937 cells,NB4 cells,K567 cells was confirmed by Flow Cytometer.ResultsCD80 was very low or no expression in patients with acute myelogenous leukemia.CD86 expressed in acute myelogenous leukemia (27.86±19.65)%,which was much higher than that in control group[(1.21±0.13)%,t＝3.55,P＜0.01].No significant changes were observed in the expression of CD86 in M4 cells(48.65±21.92)%,M5 cells(39.25±18.67)% and control group(50.20±20.31)%(P＞0.05).After the cells were cultured for 24 h and 48 h,the expression of CD86 was (30.62±5.35)% and (29.43±4.67)% in HL-60 cells ,(24.12±5.23)% and (26.56±6.54)% in U937 cells,and,(21.25±3.78)% and (23.21±6.98)% in NB4 cells (all P＞0.05).The expression of CD80 and CD86 was very low in K562 cells.ConclusionsCostimulatory molecules CD86 expressed in acute myelogenous leukemic cells in the patients with acute myelogenous leukemia and HL-60 cells,U937 cells,NB4 cells.

Effects of Leptin on the expression of CD80, CD86 and HLA-DR in human monocytes / 中国医师杂志

Objective To study the effects of Leptin on the expression of CD86 and HLA-DR in human monocytes.Methods The expression of CD86 and HLA-DR in THP-1 Cells and human primary monocytes were detected by flow cytometry.Results Expression of CD86 and HLA-DR in THP-1 cells was significantly increased after treatment with high-dose Leptin ( CD86Untreated group:8.78 ± 1.66,CD86leptin10:50.76 ± 4.29,CD86leptin100:95.20 ± 4.90; HLAUntreated group:20.75 ± 2.12,HLAleptin10:102.14 ± 5.75,HLAleptin100:104.32 ± 4.75;).The similar results were observed in human primary monocytes ( CD86Untreated group:17.91 ± 1.78,CD86leptin100:48.80 ± 3.60; HLAUntreated group:34.10 ± 2.76,HLAleptin100:88.86 ± 3.53).Conclusions By up-regulating CD86 and HLA-DR expression,Leptin might enhance the ability to present antigen in THP - 1 cells and human monocytes.

Cross-linking of CD80 and CD86 Diminishes Expression of CD54 on EBV-transformed B Cells through Inactivation of RhoA and Ras

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.

Analysis of CD86 and CD69 expression on blood lymphocytes in inflammation-induced premature mice / 第二军医大学学报

Objective: To investigate the role of Toll-like receptor 4 (TLR4) in lipopolysaccharide (LPS)-induced preterm delivery by analyzing the CD86 and CD69 expression in lymphocyte subgroups of mice. Methods: LPS was administered intraperitoneally to establish a mouse model of preterm delivery, with or without TLR4 blockade. The incidences of preterm delivery and fetal death were calculated in each group (LPS group, TLR4 blockade group, and control group). The percentages of blood CD45+ CD86+, CD3+ CD69+, CD19+ CD69+ and CD49b+ CD69+ subsets were measured by flow cytometry. Results: The incidences of preterm delivery and fetal death in LPS group were significantly higher than those in the control group (50.0% [8/16] vs 0[0/16]; 11.0%[9/82] vs 3.1%[5/163], P<0.01 or 0.05). The incidences of preterm delivery(6.3%[1/16]) and fetal death (3.9%[6/154]) in the TLR4 blockade group were significantly lower than those in the LPS group (P<0.01 or 0.05). TLR4 blockade almost completely abrogated LPS-induced increase of CD45+ CD86+, CD3+ CD69+ and CD49b+ CD69+ cell proportions (P<0.01). Conclusion: Interaction between LPS and its receptor TLR4 triggers the mobilization of CD86+ dendritic cells, which subsequently activates blood T cells and NK cells and plays an important role in preterm delivery.

Expressions of IL-10, IL-23 and CD86 in lesions of epidermodysplasia verruciformis / 中华皮肤科杂志

Objective To measure the expressions of IL-10, IL-23 and CD86 in lesions of epidermodysplasia verruciformis (EV), and to explore the relationship between cellular immune abnormality and EV pathogenesis. Methods Immunohistochemistry was used to measure the expressions of IL-10, IL-23 and CD86 in tissue samples from 10 patients with EV and 10 normal human controls. Results Three cytokines were observed in all the samples of EV, with the expression score ranging from 3 to 6 and expression intensity from moderate to high. However, of the control specimens, only 1 was positive for IL-10 with the expression score being 3, and expression intensity being moderate. Conclusion The pathogenesis of epidermodysplasia verruciformis may be correlated with the expression abnormality of some cytokines secreted by keratinocytes.

Expression and significance of CD80/CD86 in renal tissue of lupus nephritis / 中华内科杂志

Objective To measure the expression of CD80 and CD86 in renal tissue of lupus nephritis (LN) and explore its mechanism in the development of LN.Methods Forty-nine patients with active LN and 9 patients with minor glomerular abnormalities tissues as controls were studied.The expression of CD80, and CD86 in renal tissues was detected by immunohistochemical methods.Results CD86 was expressed extensively in glomerulus, periglomerular area, tubular epithelial cells and peritubular interstitium, while CD80 was expressed only in tubular epithelial cells and peritubular interstitium.Moreover, the percentage of CD+80 and CD+86 cells in tubular epithelial cells and peritubular interstitium showed a tendency to increase with tubulointerstitial damage.The expression of CD80 and CD86 in renal tissue correlated with the systemic lupus erythematosus (SLE) disease activity index score, the degree of proteinuria, creatinine clearance and anti- dsDNA antibody.Conclusions This study shows that increased CD80 and CD86 expression with the progression of tubulointerstitial lesion might play an important role in the development of lupus nephropathy, and the tubulointerstitial expression of CD80 and CD86 could potentially serve as a surrogate marker of SLE disease activity.The co-stimulatory molecules CDg, and CD86 might play an important role in the pathogenesis of LN.

Intervention with costimulatory pathways as a therapeutic approach for graft-versus-host disease

Graft-versus-host disease (GVHD) is mediated by mature donor T cells contained in the hematopoietic stem cell graft. During the development of GVHD, signaling through a variety of costimulatory receptors plays an important role in allogeneic T cell responses. Even though delivery of costimulatory signals is a prerequisite for full activation of donor T cells in the phase of their interactions with host APCs, their involvement with GVHD might occur over multiple stages. Like many other aspects of GVHD, promise of therapeutic interventions with costimulatory pathways has been gleaned from preclinical models. In this review, I summarize some of the advances in roles of costimulatory molecules in GVHD pathophysiology and discuss preclinical approaches that warrant further exploration in the clinic, focusing on novel strategies to delete pathogenic T cells.

Efecto del virus del síndrome reproductivo y respiratorio porcino (PRRS) en células dendríticas de cerdo derivadas de monocitos / Effect of porcine reproductive and respiratory syndrome (PRRS) virus on porcine monocyte-derived dendritic cells

Dendritic cells (DC) are considered the most important antigen presenting cells of the immune system. Its anatomical location (skin, mucosa and peripheral blood), the expression of receptors to recognize pathogens, the expression of co-stimulatory molecules (CD80/86), the major histocompatibility complex (MHC) class I and II, and the production of cytokines (such as IFN-α, IL-10, IL-12) confers to these cells the characteristic to regulate innate and adaptive immune responses. The objective of this work was to evaluate the effects of the porcine reproductive and respiratory virus (PRRS) in mature DC. DC were generated from blood monocytes using IL-4 and GM-CSF and were stimulated with lipopolysaccharide (LPS) to induce their maturation. The results show that the expression of CD14 and CD172a molecules in infected DC was not affected, while MHC II and CD80/86 expression was diminished. This decrease seems to affect the allogenic proliferation of lymphocytes stimulated with infected DC. On the other hand, the virus increases mRNA expression of IL-10 and TNF-α, and diminishes that for IL-1 β and IL-6. The results obtained could explain, in part, the immunophatology of the disease.

Las células dendríticas (DC) son las presentadoras de antígeno más importantes del sistema inmune. Su localización anatómica (piel, mucosas y sangre periférica), la expresión de receptores para reconocer patógenos, la expresión de moléculas de coestimulación (CD80/86), del complejo principal de histocompatibilidad (MHC) clases I y II, y la producción de citocinas (IFN-α, IL-10, IL-12), les confiere una característica única para regular las respuestas inmune innata y adaptativa. El objetivo de este trabajo fue evaluar el efecto del virus de síndrome reproductivo y respiratorio porcino (PRRS) en DC maduras. Se generaron células dendríticas a partir de monocitos utilizando IL-4 y GM-CSF y se estimularon con lipopolisacárido (LPS) para inducir su maduración. Los resultados muestran que la expresión de las moléculas CD14 y CD172a no se altera en las DC infectadas, mientras que la expresión de MHC II y CD80/86 se ve disminuida. Esta disminución parece afectar la proliferación alogénica de linfocitos estimulados con DC infectadas. Asimismo, el virus aumenta la expresión del ARNm de IL-10 y TNF-α, y disminuye la de IL-1 β e IL-6. Lo anterior explica, en parte, la inmunopatología de la enfermedad.