Fungal infection is an important clinical problem for patients with immune deficiency or immunosuppression. With deadly fungus infection case increasing, the development of antifungal vaccine attracts the attention of researchers. Dendritic cell (DC) is the unique antigen presenting cell (APC) to trigger the antifungal immune reaction, and recent studies indicate that the targeted vaccination strategy based on DC have prospective antifungal potentials. In this paper, we review the antifungal immunity mechanism and recent development of the targeted DC antifungal strategy.
ObjectiveTo explore the antitumor effect of tumor vaccine fused from dendritic cells (DC) and Walker-256 cancer cells on implanted liver cancer in rats and the related mechanism of inhibition for tumor angiogenesis. MethodsWalker-256 cancer cells and mature DC were fused by 50% polyethylene glycol method for preparation of DC-Walker-256 fusion vaccines. Implanted liver cancer models were established through operations on healthy male SD rats at the age of 6－8 weeks. All the rats were divided into four groups, and rats in each group were injected subcutanely with fusion vaccine (group), mixed cultured cells (group), simple DC (group), and PBS (blank control group), respectively. On 28 d after making model, the rats were put to death, the tumor was observed and pathological essays were prepared. All rats’ spleens were collected and prepared into lymphocyte to detect antigenic specificity cytotoxic T lymphocyte (CTL) by enzymelinked immunosorbent spot (ELISPOT) method. The expressions of VEGF, ANG-1, ANG-2, and MVD were detected by immunohistochemistry. ResultsThe numbers of rats survived in the fusion vaccine group, mixed culture cells group, simple DC group, and blank control group was 8, 5, 6, and 3, respectively. The rats in the other three groups except for fusion vaccine group were manifested as inaction, anorexia, and gloomy fur in some degree as well as ascites. The tumorigenesis was found in all survival rats except for two in the fusion vaccine group. The weight of liver tumors of rats in the fusion vaccine group 〔(32.4±9.2) g〕 was significantly lighter than that in the mixed culture cells group 〔(67.3±5.1) g, P=0.031〕, simple DC group 〔(75.0±8.3) g, P=0.019〕, and blank control group 〔(86.6±10.5) g, P=0.008〕, respectively. The number of tumorspecific CTL of rats in the fusion vaccine group was also significantly higher than that in the other three groups (P=0.019, P=0.025, and P=0.001, respectively). The MVD of tumor tissue in the fusion vaccine group was (24.12±2.32) vessels/HP, which was significantly lower than that in the mixed culture cells group 〔(40.34±1.29) vessels/HP, P=0.025〕, simple DC group 〔(42.36±3.16) vessels/HP, P=0.035〕, and blank control group 〔(56.48±5.16) vessels/HP, P=0.006〕, respectively. The MVD of tumor tissue in the mixed cultured cells group and simple DC group was similar (P=0.165), however, which was significantly lower than that in the blank control group (P=0.040 and P=0.043). The positive rate of VEGFA protein expression was 23.2% in the fusion vaccine group, which was significantly lower than that in the mixed culture cells group (42.5%, P=0.031), simple DC group (61.3%, P=0.019), and blank control group (89.6%, P=0.003), respectively. The positive rate of VEGF-A protein expression in the mixed cultured cells and simple DC groups was similar (P=0.089), however, which was significantly lower than that in the blank control group (P=0.027 and P=0.038). The positive rate of ANG-1 protein expression in the fusion vaccine group (43.2%) was not different from that in the mixed culture cells group (46.3%, P=0.292), simple DC group (51.3%, P=0.183), or blank control group (49.6%, P=0.179), respectively, and the difference of pairwise comparison in latter three groups was not significant (P=0.242, P=0.347, and P=0.182). The positive rate of ANG2 protein expression was 19.2% in the fusion vaccine group, which was significantly lower than that in the mixed culture cells group (62.3%, P=0.007), simple DC group (67.3%, P=0.005), and blank control group (71.6%, P=0.004), respectively, however, the difference of pairwise comparison in latter three groups was not significant (P=0.634, P=0.483, and P=0.379). ConclusionFused vaccine can induce CD8+ CTL aiming at tumor cells and establish the effective antitumor immunity in vivo and also downregulate the level of VEGF and ANG-2 to suppress tumor angiogenesis and thereby achieve the purpose of curing tumor.
Dendritic cells (DCs) are the most potent and specialized antigen-presenting cells (APCs) currently known, which play a crucial role in initiating and amplifying both the innate and adaptive immune responses. During the process of immune function, migration ability of DCs and the number of effector T cells which activated by DCs are closely related to the efficiency of immune function. However, because of the complexity of immune system, in the immune response process caused by the skin chronic inflammatory, much is still unknown about the dynamic changes of cell count with time. Therefore, we created a differential equations model to reflect the initial stages of the immune response process caused by the skin chronic inflammatory via setting the function and initial conditions of parameters. The results showed that the model was able to simulate migration and proliferation of cells in vivo within realistic time scales in accordance with the proliferation and migration efficiency in real terms. In addition, the preliminary model can biologically predict the realistic dynamics of DCs and T cells at different time points. All these results may provide a theoretical reference for studying the immune function of DCs as well as guiding the clinical treatment for immune related diseases further.
Objective To observe the effect of transfer of immature mouse myeloid dendritic cells （DC） generated with low-dose granulocyte-macrophage colony-stimulating factor （GM-CSF） on cardiac allograft survival. Methods Mouse DC were generated with standard doses or low doses GM-CSF from bone marrow cells, the phenotype and functional properties of these DC were compared through fluorescence-activated cell sorting（FACS） analysis and mixed lymphocyte reaction（MLR）, 1. 0 × 106 DC generated with low doses GM-CSF were administered to the recipients 7 days before transplantation, and the cardiac allograft survival were observed. Results In contrast to DC generated with standard doses, DC generated with low doses were phenotypically immature DC （CD11c＋, CD80- , CD86- , MHCⅡlow）, and induced allogeneic T cell unresponsiveness, and administration of these DC to recipients prolonged cardiac allograft survival from 6.3±1.2 days to 14.3±1.9 days. Conclusions DC generated from mouse bone marrow progenitors in low doses of GM-CSF are phenotypically and functionally immature, and prolong cardiac allograft survival when they are administered 7 clays before transplantation.
ObjectiveTo find out an effective method for amplification and purification of dendritic cells(DC) from peripheral blood of patients with pancreatic carcinoma. MethodsPeripheral blood mononuclear cells were purified from peripheral blood of health volunteers(control group,10 cases) and patients with pancreatic carcinoma (experimental group,12 cases) with incubation of granulocyte/macrophage colonystimulating factor(GMCSF) and interleukin4(IL4).The quality of DC were detected by immumofluorescence method and the expression levels of HLADR and B72 on DC were detected by flow cytometer after and before DC incubation with GMCSF and the IL4. ResultsThe expression level of HLADR and B72 of DC in experimental group were significantly less than those in control group(P＜0.01).DC in experimental group was significantly proliferated in the presence of GMCSF and IL4(P＜0.01).On day 7,the expression level of HLADR and B72 of DC in experimental group were significantly increased(P＜0.01) and there was no difference versus control group(Pgt;0.05).ConclusionIt is suggested that combination of GMCSF and IL4 can selectively and effectively enhance proliferation and immune function of DC from peripheral blood of patient with pancreatic carcinoma.
Objective To study the advances in the relationship between the number of infiltrating dendritic cells and the postoperative prognosis of digestive malignant tumor. MethodsThe literature in recent years on the relationship between the number of infiltrating dendritic cells and the postoperative prognosis of digestive malignant tumor was reviewed.ResultsThe number of infiltrating dendritic cells among esophageal cancer,and gastric carcinoma,colonic cancer and pancreatic cancer was associated with a better prognosis.Conclusion The population density of dendritic cells among the malignant tissue could be regarded as an independent indicator in estimating the postoperative prognosis of malignant tumor.
Objective To study the method of obtaining a large number of dendritic cells （DC）. To study the specific cytotoxicity T lymphocyte (CTL) effect against tumor cells initiated by DC pulsed with peptide of cancer cell. Methods Development of cells with cytologic features of DC in bone marrow cultures supplemented with granulocyte macrophage-colony stimulus factor (GM-CSF) and IL-4. Determining the DC phenotype and the specific structure by electronic microscopy. The CTL effect against pancreatic carcinoma leading by the DC pulsed with tumor cells lysate in vitro was observed. Results A large number of typical DC was proliferated by supplementing with GM-CSF and IL-4 cytokines. DC had specific cell appearance and structure, and highly expressed various cell surface molecules. TNF-α had the ability of stimulating DC mature, the mature DC had the enhancing abilities of antigen presenting and IL-12 self-secreting, as well as, expressed higher levels of CD54， MHC-Ⅱ and CD86 molecules than control group (P＜0.05). T lymphoid cell stimulated by DC without tumor antigen could not recognize and kill the target cells, only if DC pulsed with peptide of cancer cell can lead a b immune response to special tumor cells. The inhibiting ratio of CTL was significantly higher than that in other groups (P＜0.01). Conclusion Bone marrow DC has b ability of inducing special CTL against determined cancer cells after they are pulsed with tumor cell lysate. DC vaccine is probably a new immunotherapeutic method against tumor in the near future.