Mingxia Wang; Fei Qiao; Zihua Li; Qiang Wang; Zailing Shang; Junhu Hei; Xuelin Ma; Yana Wang
Abstract
Background: Different subtypes of dendritic cells (DCs) can induce different types of immune responses. Our previous study found that Echinococcus granulosus (E. granulosus) antigens (Eg.ferritin, Eg.mMDH and Eg.10) stimulated DC differentiation to different subtypes and produced different immune responses.Objective: ...
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Background: Different subtypes of dendritic cells (DCs) can induce different types of immune responses. Our previous study found that Echinococcus granulosus (E. granulosus) antigens (Eg.ferritin, Eg.mMDH and Eg.10) stimulated DC differentiation to different subtypes and produced different immune responses.Objective: To further understand whether Eg.ferritin, Eg.mMDH and Eg.10 affect the DC-mediated immune response by promoting the differentiation of monocytes to DCs.Methods: Bone marrow-derived monocytes were exposed to three antigens of E. granulosus on days 0, 3, 5, and 7. The percentage of monocyte-derived DCs (moDCs), DCs subsets, and the expression of surface molecules of DCs at different time points in different groups were assessed by flow cytometry. The levels of cytokines of IL-1β, IL-4, IL-6, IL-10, IL-13, IFN-γ, TNF-α, IL-12p70, IL-18, IL-23, and IL-27 in the cell culture supernatant were detected by multi-factorial detection technology.Results: The percentage of moDCs revealed that none of the three antigens blocked monocyte differentiation to DCs. The monocytes of 7-day-old cultures showed increased sensitivity to these antigens. The Eg.ferritin induced more mature DCs, which expressed high levels of MHC II and costimulatory molecules, and secreted Th1 cytokines. Eg10 and Eg.mMDH induced lower degrees of DC maturation, however differentiated DCs were in a semi-mature state due to low expression of MHC II and costimulatory molecules and secretion of higher Th2 and lower Th1 cytokines.Conclusion: Eg.ferritin promotes full maturation of DCs and induces Th1 immune response, whereas Eg.10 and Eg.mMDH induce semi-mature DCs producing higher levels of Th2 cytokines.
Wenjie Zhang; Shan Liu; Lin Zhao; Juncheng Wang; Meng Liu; Fengge Wang; Yuekang Xu
Abstract
Background: The functions of dendritic cells (DCs) are influenced by their intracellular metabolism, in which liver kinase B1 (LKB1) plays an important role. However, due to the difficulty in isolating the DCs, the roles of LKB1 in DC maturation and functions in tumor settings have been poorly characterized.Objective: ...
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Background: The functions of dendritic cells (DCs) are influenced by their intracellular metabolism, in which liver kinase B1 (LKB1) plays an important role. However, due to the difficulty in isolating the DCs, the roles of LKB1 in DC maturation and functions in tumor settings have been poorly characterized.Objective: To investigate the roles of LKB1 in DC functions including phagocytosis and presentation of antigens, activation, T cell differentiation, and ultimately tumor eradication.Methods: Genetic modification of Lkb1 in the DCs was made by lentiviral transduction, and their impacts on T cell proliferation, differentiation, activity, or B16 melanoma metastasis were examined by flow cytometry, qPCR, or lung tumor nodule counting.Results: LKB1 did not affect antigen uptake and presentation by the DCs, but facilitated the stimulation of T cell proliferation. Interestingly, following T cell activation, Foxp3-expressing regulatory T cells (Treg) were increased (P=0.0267) or decreased (P=0.0195) in mice injected with Lkb1 knockdown DCs or overexpressing DCs, respectively. Further exploration revealed that LKB1 inhibited OX40L (P=0.0385) and CD86 (P=0.0111) expression, and these co-stimulatory molecules enhanced Treg proliferation, and downregulated immune suppressive cytokine IL-10 (P=0.0315). Moreover, we found that the injection of the DCs with limited LKB1 expression before tumor inoculation could reduce their production of granzyme B (P<0.0001) and perforin (P=0.0042) from CD8+T cells, thereby impairing their cytotoxicity and promoting tumor growth.Conclusion: Our data suggest that LKB1 can enhance DC-mediated T cell immunity by restraining Treg development and thereby suppressing tumor growth.
Bahareh Zand; Samaneh Arab; Nasim Kheshtchin; Abazar Arabameri; Mahboubeh Ashourpour; Davoud Asemani; Ehsan Sharif-Paghaleh; Farshid Noorbakhsh; Jamshid Hadjati
Abstract
Background: Mathematical modeling offers the possibility to select the optimal dose of a drug or vaccine. Considerable evidence show that many bacterial components can activate dendritic cells (DCs). Our previous report showed that multiple doses of DCs matured with Listeria monocytogenes led to tumor ...
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Background: Mathematical modeling offers the possibility to select the optimal dose of a drug or vaccine. Considerable evidence show that many bacterial components can activate dendritic cells (DCs). Our previous report showed that multiple doses of DCs matured with Listeria monocytogenes led to tumor regression whereas multiple doses of CpG-matured DCs affected tumor reversely. Objective: To assess a combined pattern of DC vaccination proposed by a mathematical model for tumor regression. Method: WEHI164 cells were inoculated subcutaneously in the right flank of BALB/c mice. Bone marrow-derived DCs were matured by Listeria monocytogenes and CpG motifs. DCs were injected using specific patterns and doses predicted by mathematical modeling. Effector cell-mediated cytotoxicity, gene expression of T cell-related transcription factors, as well as tumor growth and survival rate, were assessed in different groups. Results: Our study indicated that the proposed mathematical model could simulate the tumor and immune system interaction, and it was verified by decreasing tumor size in the List+CpG group. However, comparing the effect of different treatment modalities on Th1/Treg transcription factor expression or cytotoxic responses revealed no advantage for combined therapy over other treatment modalities. Conclusions: These results suggest that finding new combinations of DC vaccines for the treatment of tumors will be promising in the future. The results of this study support the mathematical modelling for DC vaccine design. However, some parameters in this model must be modified to provide a more optimized therapy approach.
Piyachat Evelyn Roopngam
Saeed Daneshmandi; Mohammad Hossein Karimi; Ali Akbar Pourfathollah
Volume 14, Issue 1 , March 2017, , Pages 13-23
Abstract
Background: Mesenchymal stem cells (MSCs) and transforming growth factor-β1 (TGF-β1) molecules are well known for their immunomodulatory properties and their function in tissue regeneration and remodeling. Objectives: To evaluate the interaction of TGF-β1 engineered MSCs with T cells and ...
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Background: Mesenchymal stem cells (MSCs) and transforming growth factor-β1 (TGF-β1) molecules are well known for their immunomodulatory properties and their function in tissue regeneration and remodeling. Objectives: To evaluate the interaction of TGF-β1 engineered MSCs with T cells and dendritic cells (DCs) and their modulatory effect on the immune response. Methods: MSCs and DCs were generated from bone marrow of Balb/c mice and T cells were generated from mice lymph nodes. TGF-β1 expressing lentiviruses were used for MSCs transduction, and then these engineered MSCs were co-cultured with T cells and DCs. T cells proliferation and cytokines release and also DCs maturation, TNF-α release, and stimulation of allogeneic T cells were evaluated. Results: T cells proliferation and IFN-γ release were suppressed by TGF-β1/MSCs while IL-4 secretion was enhanced. Co-cultured DCs with TGF-β1/MSCs showed reduced expression of CD40, CD86, and MHC II and also lower level of TNF-α secretion. Co-cultured DCs could also induce lower levels of allogeneic T cells proliferation and IFN-γ release in comparison to control DCs. Conclusion: Engineered TGF-β1/MSC cells showed collaborative immune suppressive functions between TGF-β1 and MSCs to modulate T cells and DCs immune responses. We therefore suggest that TGF-β1/MSC cells could provide a promising tool for treatment of clinical conditions such as organ transplantation, GVHD, and autoimmune disorders.
Afsoon Shariat; Mohammad Hossein Karimi; Talat Mokhtariazad; Seyed Mohammad Moazzeni; Bita Geramizadeh; Seyed Ali MalekHosseini; Ramin Yaghobi
Volume 11, Issue 3 , September 2014, , Pages 153-165
Abstract
Background: Dendritic cells (DCs) are potent antigen presenting cells for triggering of the immune reaction post transplantation. These cells are centrally involved in the initiation of T cell-dependent immune responses. Objective: To compare the level of DC maturation and function in liver transplant ...
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Background: Dendritic cells (DCs) are potent antigen presenting cells for triggering of the immune reaction post transplantation. These cells are centrally involved in the initiation of T cell-dependent immune responses. Objective: To compare the level of DC maturation and function in liver transplant recipients with healthy controls. Methods: In this study, twelve peripheral blood samples were selected from six liver transplant patients and six healthy controls. After the generation of DCs from monocytes, expression levels and mean fluorescent intensity (MFI) of several DC maturation markers were evaluated using flowcytometry. Secretion of IL-6, IL-12 and IL-23 proinflammatory cytokines was determined using ELISA. Gene expressions of TLR-2, TLR-4 and IL-23 were analyzed using real-time PCR. Results: DC expression markers including CD83 (p=0.007) and CD86 (p=0.02), as well as secretion of IL-6 (p=0.02) and IL-12 (p=0.007) by DCs were significantly increased in liver transplant patients compared with healthy controls. The MFI of CD86 (p=0.009) and HLA-DR (p= 0.005) expression on DCs was also higher in patients. The expression of TLR-2 transcripts in DCs of patients was higher than that of the controls (p=0.03). Conclusion: Based on these findings, increased frequency of DCs expressing CD83 and CD86, higher expression of CD86, HLA-DR, and TLR-2 as well as elevated secretion of proinflammatory cytokines in DCs of liver transplant recipient's point to the more mature phenotype and active function of DCs in patients compared with controls.
Mohammad Hashem Soltani; Tahereh Kalantari; Mohammad Hossein Karimi; Nasrollah Erfani; Eskandar Kamali Sarvestani
Volume 9, Issue 3 , September 2012, , Pages 168-174
Abstract
Background: T helper 1 and T helper 17 cells play important roles in immunity against foreign invaders. Differentiation of these Th subsets is affected by state of maturation and cytokines that are produced by dendritic cells (DCs). Curdlan is a linear (1→3)-β- glucan and has shown activity ...
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Background: T helper 1 and T helper 17 cells play important roles in immunity against foreign invaders. Differentiation of these Th subsets is affected by state of maturation and cytokines that are produced by dendritic cells (DCs). Curdlan is a linear (1→3)-β- glucan and has shown activity against tumors and infectious agents. Objective: This study aims to investigate whether curdlan plays its role through affecting the maturation and cytokine production by DCs. Methods: DCs were isolated from the spleen of BALB/c mice by MACS method. After an overnight culture of DCs in the presence of curdlan, the expression levels of CD40, CD86, and MHC-II molecules were determined by flow cytometry. The production of cytokines involved in Th1 and Th17 cell differentiation (IL-12 and IL-6, respectively) was also evaluated by ELISA. Lipopolysaccharide (LPS) treated and untreated cells were considered as positive and negative controls, respectively. Results: The results of this study did not show a significant difference in the levels of surface expression of CD40 (p=0.82), CD86 (p=0.79), and MHC class II (p=0.84) molecules upon exposure to curdlan. However, LPS increased the intensity of CD40 expression on dendritic cells (p=0.04). In addition, it was revealed that curdlan-exposed DCs are not able to produce a significant amount of IL-6 and IL-12 cytokines. Conversely, LPS-treated DCs were able to make a significant amount of IL-12 (p=0.005). Conclusion: The results of the present study suggest that curdlan has no effect on Th1 or Th17 differentiation while LPS may induce Th1 deviation by induction of CD40 expression and IL-12 production.
Mohammad Mahdi Eftekharian; Amir Hassan Zamani; Seyed-Mohammad Moazzeni
Volume 7, Issue 2 , June 2010, , Pages 74-82
Abstract
Background: Dendritic cells (DCs) play a central role in the initiation and expansion of T cell mediated immune responses with potential immunotherapy application. The compounds which have the ability to induce immunomodulatory effects on DCs may be employed for the treatment of immunopathologic conditions ...
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Background: Dendritic cells (DCs) play a central role in the initiation and expansion of T cell mediated immune responses with potential immunotherapy application. The compounds which have the ability to induce immunomodulatory effects on DCs may be employed for the treatment of immunopathologic conditions such as autoimmune diseases. Objective: The aim of this study was to investigate the in vivo effects of calcitriol (active form of vitamin D3) on DCs. Methods: 0.1 microgram calcitriol was injected intra-peritoneally into C57BL/6 mice every other day within 3 weeks, and spleen DCs were extracted by magnetic beads. The phenotypic and functional properties of DCs were studied by flow cytometry and mixed lymphocyte reaction (MLR), respectively. Results: The expression of CD86 and MHC II, as maturation markers and costimulatory molecules were significantly decreased (p=0.028 and p=0.047, respectively) while CD11b expression, as a marker of mice myeloid DCs which mostly induces Th2 cytokine profile, was significantly increased (p=0.011). Allogeneic T cell stimulation in MLR was also significantly inhibited in comparison with the control groups (p<0.05). Conclusion: Our data indicate that in vivo calcitriol administration inhibits maturation and activation of DCs in the same manner as in vitro conditions.
Saeid Abediankenari; Yousef Yousedzadeh; Hossein Azadeh; Mohammad Vahedi
Volume 7, Issue 2 , June 2010, , Pages 83-87
Abstract
Background: Dendritic cells (DCs) are professional antigen presenting cells that have an important role in the initiation of immune response. The use of maturation factors in dendritic cell differentiation provides a promising approach in immunotherapy. Objective: In this study, we compared tumor necrosis ...
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Background: Dendritic cells (DCs) are professional antigen presenting cells that have an important role in the initiation of immune response. The use of maturation factors in dendritic cell differentiation provides a promising approach in immunotherapy. Objective: In this study, we compared tumor necrosis factor-α, polyribocytidylic acid, lipopolysacharide and CpG oligonucleotides in inducing dendritic cell maturation. Methods: We generated immature dendritic cells with GM-CSF in combination with IL-4 from peripheral blood mononuclear adherent cells and used tumor necrosis factor-α, polyribocytidylic acid, lipopolysacharide and CpG for the induction of dendritic cell maturation. CD83 maturation marker on the dendritic cells was analyzed by flowcytometry after 7 days. In addition, mixed leukocyte reaction between dendritic cells and T cells was performed by MTT proliferation assay. Results: Flow cytometry results demonstrated a comparable high level of CD83 expression on the mature dendritic cells generated by TNF-α, CpG, Poly I:C, and LPS treatment of the immature dendritic cells. However, a significantly poorer proliferation of lymphocytes cocultured with the Poly I:C-treated DCs was observed compared to the CpG-treated DCs in mixed leukocyte reaction (p=0.026). Conversely, a significantly stronger proliferation of lymphocytes was observed when cocultured with TNF-α-treated DCs compared to the LPS-treated DCs (p=0.025). Conclusion: Our results indicated that all of studied maturation inducing factors can be used in DC maturation but TNF-α and CpG were the preferred in vitro maturation factors. It is concluded that maturation of dendritic cells by CpG motif and TNF-α can be used to regulate immune responses.
Marzieh Ebrahimi; Zuhair Mohammad Hassan; Jamshid Hadjati; Parisa Hayat; Seyed Mohammad Moazzeni
Volume 6, Issue 3 , September 2009, , Pages 107-118
Abstract
Background: Tumor necrosis factor alpha (TNF-α) is a primary mediator of immune regulation and might be required in the early stages of DC development from CD34+ cells. However, details of optimal timing of exposure to TNF-α in DC development process in monocytes or non-purified hematopoitic ...
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Background: Tumor necrosis factor alpha (TNF-α) is a primary mediator of immune regulation and might be required in the early stages of DC development from CD34+ cells. However, details of optimal timing of exposure to TNF-α in DC development process in monocytes or non-purified hematopoitic cells are still lacking and clear benefits of this approach to the development of DCs remain to be validated. Objective: To evaluate the effect of early and late exposure to TNF-α on DC devel-opment from non-purified cord blood mononuclear cells. Methods: To define the ef-fects of early exposure to TNF-α on cord blood mononuclear cells, we cultured UCB-MNC in the presence of SCF, Flt3L, GM-CSF and IL-4 for 14 days and matured them for an extra 4 days. TNF-α was added on day 0, 7 and 14 in TNF-α + group, and only on day 14 in TNF-α - group where it was used only as a maturation factor. Results: Immediate exposure to TNF-α was shown to: (1) enhance the survival of cells in the first week of culture; (2) produce mature DCs with higher maturation markers (CD80, CD83, CD86 and HLA-DR); and (3) increase secretion of IL-12 by mature DCs. In contrast, delayed exposure to TNF-α stimulate mature DCs with less purity producing a high level of IL-10 and a low level of IL-12. Conclusion: We developed a simple, easy and cost effective method to generate DCs from non-fractionating mononuclear cells in this study. Also we confirm the presence of a large number of functional DCs under inflammatory conditions, where local concentrations of TNF-α were high.
Saeid Abediankenari; Davoud Shaker; Farshideh Abedian; Arazmohammad Mirabi
Volume 6, Issue 2 , June 2009, , Pages 61-66
Abstract
Background: Dendritic cells (DC) are a key regulator of the immune response, and interferon- beta (IFN-β) is considered an immunomodulatory molecule for DC. Objective: The purpose of this study was to evaluate the ability of IFN-β treated DC to induce cytokine secretion by CD4+ T cells. Methods: ...
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Background: Dendritic cells (DC) are a key regulator of the immune response, and interferon- beta (IFN-β) is considered an immunomodulatory molecule for DC. Objective: The purpose of this study was to evaluate the ability of IFN-β treated DC to induce cytokine secretion by CD4+ T cells. Methods: Dendritic cells were generated from blood monocytes with granulocyte-monocyte colony-stimulating factor and interleukin-4 with or without IFN-β. We analyzed the production of CD4+ T helper cytokines (IL-17, IFN- γ and IL-10) in the supernatant of the dendritic cell-T cell co- cultures by ELISA. We also studied the effects of HLA-G and costimulatory molecules on immature and mature DC. Results: IFN-γ and IL-17 decreased significantly in the presence of HLA-Gbearing DC compared to control cultures (p<0.05). Conclusion: Using the mixed leukocyte reaction, we found that DC treated with IFN-β mediated the inhibition of T cell activation via cytokine production. We conclude that this is important for preventing overactivation of the immune system.
Maryam Roudbary; Shahla Roudbar Mohammadi; Mahmood Bozorgmehr; Seyed Mohammad Moazzeni
Volume 6, Issue 2 , June 2009, , Pages 67-74
Abstract
Back ground: Candida albicans is a member of the normal human microflora. C. albicans cell wall is composed of several protein and carbohydrate components which have been shown to play a crucial role in C. albicans interaction with the host immune system. Major components of C. albican cell wall are ...
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Back ground: Candida albicans is a member of the normal human microflora. C. albicans cell wall is composed of several protein and carbohydrate components which have been shown to play a crucial role in C. albicans interaction with the host immune system. Major components of C. albican cell wall are carbohydrates such as mannans, β glucans and chitins, and proteins that partially modulate the host immune responses. Dendritic cells (DC), as the most important antigen-presenting cells of the immune system, play a critical role in inducing immune responses against different pathogens. Objective: We investigated the effect of the cell wall protein fraction (CPF) of C. albicans on DC maturation. Methods: The CPF of C. albicans cells was extracted by a lysis buffer containing sodium dodecyl sulphate, 2-mercaptoethanol and phosphate-buffered saline. The extract was dialyzed and its protein pattern was evaluated by electrophoresis. Dendritic cells were purified from Balb/c mice spleens through a three-step method including mononuclear cell separation, as well as 2-h and overnight cultures. The purified CPF was added at different concentrations to DC. The purity and maturation status of DC were determined by flow cytometry using monoclonal antibodies against CD11c, MHC-II, CD40 and CD86. Results: Treatment of DC with 10 μg/ml of CPF increased the expression of maturation markers including MHC-II, CD86 and CD40 on DC compared to the control group. Conclusion: In this study we used C. albicans CPF with the molecular weight of 40-45 kDa for pulsing and maturation of dendritic cells. Since according to our results CPF significantly increased the expression of maturation markers on DC, we suggest that CPF may act as an efficient immunomodulator, or may be used as a potential adjuvant to boost the host immune system against infections.
Padideh Ebadi; Mohammad Hossein Karimi; Ali Akbar Pourfathollah; Saheb Ghadam Lotfi; Zahra Soheila Soheili; Shahram Samiee; Smerdis Hajati; Fatemeh Nadali; Bita Geramizadeh; Seyyed Mohammad Moazzeni
Volume 6, Issue 1 , March 2009, , Pages 1-11
Abstract
Background: Dendritic cells (DCs) are ideal accessory cells in the field of gene therapy. Delivery of DNA and siRNA into mammalian cells is a useful technique in treating various diseases caused by single gene defects. Selective gene silencing by small interfering RNAs (siRNAs) and antisense oligodeoxynucleotides ...
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Background: Dendritic cells (DCs) are ideal accessory cells in the field of gene therapy. Delivery of DNA and siRNA into mammalian cells is a useful technique in treating various diseases caused by single gene defects. Selective gene silencing by small interfering RNAs (siRNAs) and antisense oligodeoxynucleotides (ODN)s is an efficient method for the manipulation of cellular functions. An efficient, functional delivery system with no toxicity problems would be attractive. Objective: We compared two commercially available cationic lipids, Lipofectamine and FuGENE6, in the delivery of both siRNA and antisense ODNs into mice spleen-derived DCs. Methods: Cellular uptake was measured by the means of fluorescein-labelled non-silencing siRNA and antisense ODNs as a model system using flow cytometry. Cytotoxicity of the two delivery systems was compared with propidium iodide and annexin-V staining, and quantified with flow cytometry. The efficiency of our oligonucleotide delivery systems was compared by measuring CD40 expression by flow cytometry. Results: CD40 expression in DCs was 38%. After siRNA transfection by Lipofectamine, CD40 expression decreased to 13%, and after transfection by FuGENE6, it decreased to 18%. The difference was statistically significant. CD40 down regulation in DCs transfected with the two different antisense sequences by Lipofectamine was 21% and 23%, and down regulation after transfection by FuGENE6 was 19% and 18%, respectively. The differences were not statistically significant. The effects of siRNA and antisense ODNs were specific. Conclusion: Lipofectamine was a more potent delivery system in siRNA effect, followed by FuGENE6. There was no significant difference between Lipofectamine and FuGENE6 as a delivery system of antisense ODNs.
Masoumeh Khamisabadi; Samaneh Arab; Masoumeh Motamedi; Nematollah khansari; Seied Mohammad Moazzeni; Zahra Gheflati; Jamshid Hadjati
Volume 5, Issue 1 , March 2008, , Pages 36-44
Abstract
Background: The use of dendritic cells (DCs) as a cellular adjuvant provides a promis-ing approach in immunotherapy of cancer. It has been demonstrated that Listeria mono-cytogenes activated DCs pulsed ex vivo with tumor antigens trigger a systemic Th1-biased specific immune response and a single dose ...
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Background: The use of dendritic cells (DCs) as a cellular adjuvant provides a promis-ing approach in immunotherapy of cancer. It has been demonstrated that Listeria mono-cytogenes activated DCs pulsed ex vivo with tumor antigens trigger a systemic Th1-biased specific immune response and a single dose of this vaccine will cause a consider-able anti tumor immunity. Objective: The present study was designed to evaluate the ability of multiple doses of tumor antigen-pulsed DCs, matured in the presence of Lis-teria monocytogenes components in induction of a potent anti-tumor response and the prevention of tumor formation in an experimental model. Methods: Bone-marrow de-rived DCs (BMDCs) were cultured in the presence of GM-CSF and IL-4. After 5 days, tumor lysates with/without Listeria monocytogenes lysate were added to the culture media for another 2 days. Mice received mature and tumor antigen pulsed dendritic cells subcutaneously in 3 groups. Tumor growth was monitored and two weeks after immu-notherapy, cytotoxic activity of CD8+ T cells was evaluated in different groups. Re-sults: According to the findings, repeated doses of vaccine did not lead to a significant increase in the activity of cytotoxic T cells and decreased tumor growth of immunized animals. Conclusion: The current study suggests that increased doses of vaccine do not have sufficient efficiency for prevention of tumor induction. Generation of T regulatory responses upon repeated doses of such vaccines should be considered in future investi-gations.
Ahmad Jalili
Volume 4, Issue 3 , December 2007, , Pages 127-144
Abstract
Dendritic cells (DCs) are antigen presenting cells with unique capability to take up and process antigens in the peripheral blood and tissues. They subsequently migrate to draining lymph nodes where they present these antigens and stimulate naive T lympho-cytes. During their life cycle, DCs go through ...
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Dendritic cells (DCs) are antigen presenting cells with unique capability to take up and process antigens in the peripheral blood and tissues. They subsequently migrate to draining lymph nodes where they present these antigens and stimulate naive T lympho-cytes. During their life cycle, DCs go through two maturation stages and are referred to as immature and mature cells, respectively. While immature DCs are very good at cap-turing antigens, mature DCs are suitably equipped to present antigens to T cells and to initiate an immune response. DCs with different phenotypes serve as sentinels in nearly all tissues including the peripheral blood, where they are continuously exposed to anti-gens. Very small numbers of activated DCs are extremely efficient at generating im-mune response against viruses, other pathogens and in experimental models of tumors. Protection against infectious microorganisms and probably against tumors is provided by complex interactions of the innate and adaptive immune systems. For the initiation to occur, pathogens must first be recognized as a “danger”. DC possesses specific recep-tors to detect such danger signals. The unique immune-stimulating properties of DC and the feasibility of manipulating their function arouse much enthusiasm and hold great promise for the treatment of cancer. Early clinical trials showed that DC can induce immune responses in cancer patients. Nonetheless, cancer treatments based on DC ad-ministration require further studies that will optimize this promising treatment modality.
Mahyar Nouri-Shirazi
Volume 4, Issue 1 , March 2007, , Pages 1-14
Abstract
Dendritic cells (DCs) are a heterogeneous family of professional APCs involved in priming adaptive immune responses. Donor DCs (direct pathway of allorecognition) and recipient DCs presenting processed donor major histocompatibility complex (MHC) as peptides (indirect pathway of allorecognition) participate ...
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Dendritic cells (DCs) are a heterogeneous family of professional APCs involved in priming adaptive immune responses. Donor DCs (direct pathway of allorecognition) and recipient DCs presenting processed donor major histocompatibility complex (MHC) as peptides (indirect pathway of allorecognition) participate actively in graft rejection by stimulating recipient T cell responses following organ transplantation. Recent studies have shown that DCs also play a central role in inducing and maintaining tolerance to self antigens (Ags) through deletion, anergy, and regulation mechanisms. It is easy to see how the remarkable functional plasticity of DCs renders them attractive therapeutic targets for immune modulation. Indeed, in the past few years, successful outcomes in rodent models have built the case that DC-based therapy may provide a novel approach to transplant tolerance. Ongoing research into our understanding of the mechanisms whereby DCs promote tolerance in the steady-state, together with development of biologi-cally, pharmacologically and genetically manipulated ex vivo DCs to mimic/enhance their natural tolerogenicity, should warrant the success of these experimental DCs in establishing long-term allograft survival.
Nahid Naderi; Ali Akbar Pourfathoolah; Mahin Nikougoftar; Kamran Alimoghadam; Ardeshir Ghavamzadeh; Seyed Mohammad Moazzeni
Volume 2, Issue 1 , March 2005, , Pages 21-28
Abstract
Background: Dendritic cells (DCs) are the most potent stimulators of primary T cell responses and play a key role in immune reactions after stem cell transplantation. Very little is known about the cord blood (CB) dendritic cells and their potential involvement in the low incidence and lower severity ...
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Background: Dendritic cells (DCs) are the most potent stimulators of primary T cell responses and play a key role in immune reactions after stem cell transplantation. Very little is known about the cord blood (CB) dendritic cells and their potential involvement in the low incidence and lower severity of acute graft-versus-host disease after CB transplantation. Objectives: The aim of this study was the isolation of cord blood and peripheral blood dendritic cells and comparison of their functional competence and determination of their probable role in graft versus host disease after stem cell transplantation. Methods: In this study, fresh peripheral blood DCs (PBDCs) were enriched as HLA-DR + cells, lacking the CD3, CD11b, CD14, CD16, CD19 and CD56, using immunomagnetic bead depletion. For cord blood dendritic cells (CBDCs) enrichment CD34 + and CD66b+ cells were needed to be depleted too. Immunomagnetically enriched PB/CB dendritic cells were co-cultured with adult T lymphocytes and cell proliferation was measured by 3H-thymidine incorporation. Results: Results showed that CBDCs were significantly poor stimulators of the mixed leukocyte reaction as compared with PBDCs (P < 0.05). Conclusion: The demonstrated impairment of CBDCs function could be of importance in interpretation of the low incidence and milder severity of graft-versus-host disease (GVHD) in umbilical CB transplantation compared with peripheral blood or bone marrow stem cell transplantation.
