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Objective:To explore the Epstein-Barr virus (EBV) latent infection membrane protein (LMP) 1 or LMP2 specific T cell immune response and clinical significance in stage III-IVa nasopharyngeal carcinoma (NPC), aiming to provide ideas and evidence for immunotherapy in NPC.Methods:Fifty-nine NPC patients admitted to the Affiliated Tumor Hospital of Xinjiang Medical University from February 2018 to October 2020 for primary treatment were collected. Peripheral blood monocytes (PBMCs) were stimulated by LMP antigen. Intracellular cytokine staining and flow cytometry were applied to study the expression levels of IL-2, IL-13, interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) from CD4 + T and CD8 + T cells, and then analyzed in conjunction with clinical factors. Results:The positive rates of total PBMCs to LMP1 and LMP2 in NPC patients were different. The positive rate of LMP1 specific CD4 + T cells was statistically higher in stage T 3-T 4 NPC than that in stage T 1-T 2 (51.0% vs. 10.0%, P=0.042). There were also differences in the expression of cytokines between LMP1 and LMP2, CD4 +T cells and CD8 +T cells. Survival analysis showed the 2-year and 3-year overall survival (OS) rates were 91.5% and 88.2%, and the 2-year and 3-year progression-free survival (PFS) rates were 83.3% and 75.3%. Univariate analysis suggested that smoking history, male and LMP1 stimulated IL-13 positive expression in CD4 + T cells affected the disease progression ( P=0.026, 0.045 and 0.006); multivariate analysis showed LMP1 stimulated IL-13 positive expression in CD4 + T cells and smoking history were the independent prognostic factors affecting PFS ( P=0.017, 0.019). Conclusions:LMP1 and LMP2 generate specific T-cell immune response in PBMCs of NPC patients, with differential expression in two T-cell subsets. LMP1 and LMP2 specific T cell immune response is associated with primary tumor size and metastatic lymph node volume. LMP1 stimulated IL-13 positive expression in CD4 + T cells and smoking history affects the disease progression.
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Chronic virus infection leads to the functional impairment of dendritic cells (DCs) as well as T cells, limiting the clinical usefulness of DC-based therapeutic vaccine against chronic virus infection. Meanwhile, B cells have been known to maintain the ability to differentiate plasma cells producing antibodies even during chronic virus infection. Previously, alpha-galactosylceramide (alphaGC) and cognate peptide-loaded B cells were comparable to DCs in priming peptide-specific CD8+ T cells as antigen presenting cells (APCs). Here, we investigated whether B cells activated by alphaGC can improve virus-specific T cell immune responses instead of DCs during chronic virus infection. We found that comparable to B cells isolated from naive mice, chronic B cells isolated from chronically infected mice with lymphocytic choriomeningitis virus (LCMV) clone 13 (CL13) after alphaGC-loading could activate CD1d-restricted invariant natural killer T (iNKT) cells to produce effector cytokines and upregulate co-stimulatory molecules in both naive and chronically infected mice. Similar to naive B cells, chronic B cells efficiently primed LCMV glycoprotein (GP) 33-41-specific P14 CD8+ T cells in vivo, thereby allowing the proliferation of functional CD8+ T cells. Importantly, when alphaGC and cognate epitope-loaded chronic B cells were transferred into chronically infected mice, the mice showed a significant increase in the population of epitope-specific CD8+ T cells and the accelerated control of viremia. Therefore, our studies demonstrate that reciprocal activation between alphaGC-loaded chronic B cells and iNKT cells can strengthen virus-specific T cell immune responses, providing an effective regimen of autologous B cell-based therapeutic vaccine to treat chronic virus infection.
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Animals , Mice , Antibodies , Antigen-Presenting Cells , B-Lymphocytes , Clone Cells , Cytokines , Dendritic Cells , Glycoproteins , Lymphocytic choriomeningitis virus , Natural Killer T-Cells , Plasma Cells , T-Lymphocytes , ViremiaABSTRACT
Objective To investigate the accumulation and maturation status of pulmonary conventional dendritic cells (cDCs) in the early phase of acute lung injury (ALI),and to explore the way of the inflammatory responses and lung injury modulated by cDCs in vivo.MethodsMale C57BL/6 mice were randomly ( random number) divided into the normal control group,6 h-ALI group and 24 h-ALI group.Murine model of ALI was made by intra-tracheal administration of lipopolysaccharide (LPS) and lung specimens were taken 6 h or 24 h later.The accumulation and maturation status of pulmonary cDCs were assessed by flow cytometry.IL-6 and TNF-α were quantified to evaluate the lung inflammation.Transcription factors T-bet/GATA-3 mRNA ratio was determined to estimate the balance between Th1/Th2 responses.IFN-γand IL-4 were quantified to evaluate Thl-specific and Th2-specific cytokine production respectively.Lung injury was estimated by lung wet weight/body weight ratio (LWW/BW) and histopathological assessment.Comparison between groups was performed using one -way ANOVA.ResultsCompared with normal control group,LPS challenge resulted in higher level of IL-6 and TNF-α,increased LWW/BW ratio and significant histopathological changes (P ＜0.01 ).The accumulation and maturation of pulmonary cDCs in 6 h-ALI group were significantly increased after LPS challenge (P ＜0.01 ),while the accumulation and maturation of pulmonary cDCs in 24 h-ALI group were significantly lower than that in 6 h-ALI group ( P ＜0.01 ).Compared with normal control group,the expression of T-bet mRNA in 24 h-ALI group was markedly enhanced ( P ＜ 0.01 ) and the production of IFN-γ was increased as well ( P ＜ 0.01 ).ConclusionsThe accumulation and maturation of pulmonary cDCs peaked within 24 h after LPS challenge,pulmonary cDCs may initiate and amplify acute lung inflammation of ALI by enhancing the Th1 immune response and ensuing cytokine production.
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@#ObjectiveTo investigate whether immune adjuvant can enhance the immunity of dendritic cell vaccine against murine breast cancer. Methods4 groups of mice with tumor are injected saline, immume adjuvant, dendritic cell (DC) vaccine and DC vaccine coupled with immune vaccine, respectively. Tumor volume and weight are measured 21 d later.ResultsThe tumor size in the DC vaccine coupled with immune vaccine group was significantly small compared with control group (P=0.001) and the DC vaccine group (P=0.047).ConclusionImmune adjuvant can enhance the immunity of dendritic cell vaccine against murine breast cancer.
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0.05).CD3~+,CD4~+,CD4~+/ CD8~+ in A group on the 8th day were higher(P0.05) than those on the 1st day.Compared to B group,CD3~+,CD4~+,CD4~+/ CD8~+ in A group on the 8th day were increased significantly(P
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The regulation of immune response is affected by several factors in order to maintain homeostasis.Indoleamine 2,3-dioxygenase(IDO) is a tryptophan-catabolizing enzyme expressed by different types of APC,including macrophages and dendritic cells.IDO activity leads to regulatory effects on T cells,which are mediated by tryptophan depletion in specific local tissue microenvironments,the production of proapoptotic metabolites,and inhibition of T-cell clone proliferation through regulatory T cells.IDO plays an important role in protecting the allogeneic fetus from rejection,the development of autoimmune diseases,allograft rejection,and cancer.So regulation of IDO activity may offer a novel drug-based strategy to treat immune-related diseases.
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BACKGROUND AND OBJECTIVE: Normal gut immune response to ingestive food proteins is induction of immune tolerance rather than sensitization, even in atopic individuals. Very restricted kinds of food antigens have been known to cause allergic sensitization in humans. To evaluate the differences of systemic T-cell immune responses to sensitized antigen and regular chow-protein, we performed this study. SUBJECTS AND METHODS: Eight naive female, 5-week-old C3H/HeJ mice were grown under the regular mouse chow feeding condition for 4 weeks. During that period, Group I mice were sensitized with buckwheat extract(1mg/dose) mixed with cholera toxin(10 microgram/dose) by intragastric administration at day1, 2, 3, 7, and 21. The sera were obtained at weekly intervals to measure buckwheat-specific and chow-protein-specific IgE, IgG1 and IgG2a antibodies. Splenocyte proliferation assays and cytokine productions were evaluated with buckwheat. chow-protein. and Con A stimulation. Levels of antibodies (IgE, IgG1, IgG2a) and cytokines (IL-4, IL-10, IL-12, INF-gamma were measured by ELISA. RESULTS: The levels of buckwheat specific IgE, IgG1 and IgG2a were markedly increased in Group I mice, but not in Group II mice. Chow-protein specific IgE and IgG1 antibodies were not increased in both groups of mice. The degrees of buckwheat-specific and chow-protein-specific splenocyte proliferations showed low-grade(SI: 6.68 and 4.48. respectively) compared to those by Con A stimulation(SI : 58). Buckwheat stimulated IL-4 productions were markedly increased in Group I mice, which were higher than Con A stimulated production. INF-gamma production was increased in Group I mice by buckwheat stimulation, and in both groups of mice by Con A stimulation. IL-12 production was shown in Con A stimulated culture supernatants in both groups of mice, but in Group I mice with buckwheat stimulation. IL-10 productions were increased in Group I mice with buckwheat, Con A, and chow-protein stimulations, furthermore, markedly increased IL-10 levels were also shown in chow-protein stimulated splenocyte cultures in both groups of mice. CONCLUSION: While Th1 and Th2 immune responses were induced by intragastricly sensitized buckwheat extract, only regulatory immune responses were dominated by regular chow proteins in this system. The minimum ability of chow-protein specific splenocyte proliferation was preserved and IL-10 was the unique cytokine produced by chow-protein simulation.
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Animals , Female , Humans , Mice , Antibodies , Cholera , Cytokines , Enzyme-Linked Immunosorbent Assay , Fagopyrum , Immune Tolerance , Immunoglobulin E , Immunoglobulin G , Interleukin-10 , Interleukin-12 , Interleukin-4 , T-LymphocytesABSTRACT
Objective To analyze the relationship between serum Th1/Th2 cytokines levels and autoantibodies against thyroid, and explore the role of Th1/Th2 cellular immunity imbalance in the pathogenesis of autoimmune thyroid diseases(AITD). Methods 21 patients with Graves'desease(GD), 18 cases with Hashimoto's thyroiditis(HT), 17 cases with non-toxic nodular goiter(NTNG) and 20 healthy subjects were enrolled in this study. The serum concentrations of their Th1 cytokines (IFN-?,IL-2) and Th2 cytokines (IL-4,IL-10) were assayed by ELISA. The serum levels of their thyrotropin receptor antibodies(TRAb), thyroglobulin antibodies (TGAb) and thyroid peroxidase antibodies(TPOAb) were measured by routine methods. The relationship between the serum Th1, Th2 cytokines levels and serum TRAb, TGAb, TPOAb levels were analyzed. Results The serum levels of IL-4 and IL-10 in patients with GD were significantly higher than those in patients with HT,NTNG and healthy subjects(P
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Objective:To study the effect of Eupolyphaga Sinensis Walker (ESW) on red blood cell immune adherence (RCIA) in mice model with blood-deficiency by Cyclophosphamide , aimingatfurther research on the mechanism of blood stasis syndrome and promoting blood circulation and removing blood stasis.Methods:This model was made in mice by i.p. cyclophosphamide (0.01 g/kg).It has been observed that how the influence of ESW on the function of red cell immune adherence. The serum anticardiolipin antibodies (ACA),ACA-IgG?ACA-IgA and ACA-IgM levels were measured by using enzymelinked immunosorbent assay (ELISA). The mice body weight were weighted before model and after model and glandular weight were weighted. The serum levels of trace element zinc calcium were determined in healthy mice.Results:The results showed there is a decline in garland rate of red blood cell C3b receptors (RBC-C3bRR) in mice when animal model of Blood - deficiency by cyclophosphamide (0.01 g/kg) form, the serum ACA-IgG and ACA-IgA levels were markedly elevated,while mice body weight and spleen thymus weight markedly depressed. ESW (25 g/kg) increased RBC-C3bRR in the mice model with Blood-deficiency,restified the mice model body weight loss by cyclophosphamide, increased spleen thymus weight .ESW (25 g/kg) increased serum zinc calcium level in the normal mice.Conclusion:ESW increases activity of CR 1 of red blood cells and RCIA, inhibits serum ACA-IgG and ACA-IgA.ESW enhances serum zinc calcium level, that can be a good biological pharmacodynamics.
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Inthis study, the DNA fragment encoding the regions Ⅰ to Ⅱ of CSP gene from Plasmodium falciparm isolate FCC1/HN was cloned into an. expression vector pcDNA3 contained cytomegalovius (CMV) and transformed into human Hela cell line. The expressed protein PfCSP (condidate vaccine) was used to immunize BALB/c mice by subcutaneous、 intravenous or intraperitoneal administration respectively. The splenocyte of BALB/c mice immumized with the condidate vaccine released significantly IL-2 and IFN-γ following stimulation with this vaccine. It is associated with increase of the splenic T lymphocyte proliferation stimulated by this vaccine and enhancement of NK cell killing activity in the former studies. These results suggested that the vaccine could stimulate T cell response and enhance the cell-mediated immunity.
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Objective: To discuss the feasibility of immune tolerance in rat small bowel trans-plantation induced by immature dendritic cells isolated from SD and Wistar rat. Methods: Dendritic cells isolated from liver or bone marrow of inbred strain Wistar and SD rat were cultured for five to nine days. A week before operation, the recipient rats were injected 2?106 inmature DCs from vena dorsalis penis and observed. The models of heterotopic small bowel transplantation (SBT: SD→ Wistar)were established. Acute immuno- rejection levels were evaluated by HE. Results: Varying degrees of rejection were observed in 3, 5, 7 days after operation. Conclusion: Immature DC can induce allogenic immunological tolerance of rat small bowel transplantation.
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Objectives:To observe the effects of enteral nutrition on cell immune in patients with acute renal failure. Methods:The changes of cell immune were compared in 22 patients with acute renal failure before and after EN treatment. Results:There were significant improvements in cell immune after 10 days of EN. CD3,CD4,CD4/CD8 and NK acitivity( P
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We established a new method, the E-ELISA, to detect red-cell immune adherence (RCIA) activity and the value of immune complexes on the surface of red cell. This method has a good specificity, reproducibility and easily perform, with a sensitivity of 31.25ng/100ul. Fifty samples from normal human were determined. The RCIA activity was 5445 (3.73 ? 0.22 LgG,ngAHG/10~7RBC and the value of immune complexes on the surface of red cell was 234.7(2.37 + 0.21LgG)ngAHG/10~7RB C. We likely suggest that this method is a good tool for study of immune fanction of erythrocytes
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Objective:To study the activity of immunological regulative function of red blood cells of the patients with chronic renal failure.Methods:The proliferative reaction of the erythrocyte promoting lymphocyte was detected in CRF patients and healthy persons with MTT colorimetry,in which the normal person's lymphocyte as the target cell and the erythrocyte as the stimulating cell.Results:It was found that the healthy persons of control group had obvious proliferative reaction of the erythrocyte promoting lymphocyte(promoting rate:57.3%?10.2%),while the 36 CRF patients had lower proliferative activity(promoting rate:32.7%?7.8%,P