Shahid Waseem; Kashif-Ur-Rehman -; Ramesh Kumar; Tariq Mahmood
Volume 13, Issue 1 , March 2016, , Pages 1-8
Abstract
Background: Falciparum malaria is a severe health burden worldwide. Antigen presenting cells are reported to be affected by erythrocytic stage of the parasite. Malarial hemozoin (HZ), a metabolite of malaria parasite, has adjuvant properties and may play a role in the induction of immune response against ...
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Background: Falciparum malaria is a severe health burden worldwide. Antigen presenting cells are reported to be affected by erythrocytic stage of the parasite. Malarial hemozoin (HZ), a metabolite of malaria parasite, has adjuvant properties and may play a role in the induction of immune response against the parasite. Objective: To determine the immunological impact of hemozoin on the capacity of innate immune cells maturation. Methods: Plasmodium falciparum (F32 strain) was cultured in O+ blood group up to 18% parasitemia. Natural hemozoin was extracted from infected red blood cells. Murine bone marrow derived macrophages and myeloid dendritic cells were stimulated with 4 ߤg/mL or 40 ߤg/mL of synthetic hemozoin (β-hematin) or natural hemozoin. We assessed the immunomodulatory role of synthetic or natural hemozoin in vitro by flowcytometric analysis. Results: The maturation markers MHCII, CD80 and CD86 were significantly upregulated (p<0.05) on the surface of murine bone marrow derived macrophages or myeloid dendritic cells. Data confirmed the potential of macrophages or myeloid dendritic cells, through hemozoin activation, to establish an innate immune response against malaria parasites. Conclusion: Both synthetic and natural hemozoin are potent inducers of cellular immunity against malaria infection. However, natural hemozoin is a stronger inducer as compared to synthetic hemozoin.
Mahboobeh Razmkhah; Nadieh Abedi; Ahmad Hosseini; Mohammad Taghi Imani; Abdol-Rasoul Talei; Abbas Ghaderi
Volume 12, Issue 1 , March 2015, , Pages 1-15
Abstract
Background: Adipose derived stem cells (ASCs) provoke the accumulation and expansion of regulatory T cells, leading to the modulation of immune responses in tumor microenvironment. Objective: To assess the effect of tumoral ASCs on the trend of regulatory T cells differentiation. Methods: Peripheral ...
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Background: Adipose derived stem cells (ASCs) provoke the accumulation and expansion of regulatory T cells, leading to the modulation of immune responses in tumor microenvironment. Objective: To assess the effect of tumoral ASCs on the trend of regulatory T cells differentiation. Methods: Peripheral blood naïve CD4+ T cells were co-cultured with ASCs derived from breast cancer or normal breast tissues. In separate cultures peripheral blood naïve CD4+ T cells were exposed to the culture supernatants of ASCs. Results: Generation of CD4+CD25+Foxp3+ and CD4+CD25- Foxp3+ Treg subsets was observed after coculture of naïve CD4+ T cell with either ASCs or the related supernatant. The percentage of CD4+CD25+Foxp3+ cells increased after exposing naïve CD4+ T cells to both ASCs and their supernatants while augmentation of CD4+CD25-Foxp3+ subset mostly depended on the presence of ASCs. Similarly, upregulation of FoxP3 molecule was more significant in condition of cell to cell contact. IL-4 and IL-10 were up-regulated in the cocultured naïve CD4+ T cells after exposure to ASCs/supernatant while IFN-γ was down-regulated in the presence of ASCs. Conclusion: Accordingly, ASC may act as one of the major players in tumor site with immunomodulatory effects, which may mostly be carried out through direct cellcell interaction.
Fathollah Kalantar; Mohammad Hossein Dabbaghmanesh; Emanuela Martinuzzi; Mohsen Moghadami; Zahra Amirghofran
Volume 11, Issue 1 , March 2014, , Pages 1-12
Abstract
Background: Type 2 diabetes (T2D) is a chronic metabolic disorder in which beta-cells are destroyed. The islet amyloid polypeptide (IAPP) produced by beta-cells has been reported to influence beta-cell destruction. Objective: To evaluate if IAPP can act as an autoantigen and therefore, to see if CD8 ...
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Background: Type 2 diabetes (T2D) is a chronic metabolic disorder in which beta-cells are destroyed. The islet amyloid polypeptide (IAPP) produced by beta-cells has been reported to influence beta-cell destruction. Objective: To evaluate if IAPP can act as an autoantigen and therefore, to see if CD8 + T-cells specific for this protein might be present in T2D patients. Methods: Peripheral blood mononuclear cells (PBMC) were obtained from human leukocyte antigen (HLA)-A2 + T2D patients and non-diabetic healthy subjects. Cells were then screened for peptide recognition using ELISPOT assay for the presence of IFN-γ producing CD8 + T-cells against two HLA Class I-restricted epitopes derived from IAPP (IAPP 5-13 and IAPP9-17) and common viral antigenic minimal epitopes Flu MP 58-66, CMV495–503, EBV280–288 and HIV77–85 as controls. Results: A total of 36.4% of patients and 56.2% of healthy subjects showed a response against IAPP 5-13 peptide. No significant difference in response against this peptide was noted between the patients and the healthy donors. With respect to peptide IAPP 9-17, although healthy subjects showed a higher mean number of spot forming cells than the patients, the difference was not significant; 36.4% of patients and 37.5% of controls responded to this peptide. The response of healthy subjects to the common viral peptides was stronger than that of the patients, though the result was not significant. Conclusions: It is unlikely that IAPP would be a target for CD8+ T-cells in diabetic patients; however, the trend observed toward a lower response of T2D patients against IAPP and common viral peptides may imply a decreased immune response in these patients.
Nafiseh Esmaili; Hossein Mortazavi; Sheyda Chams-Davatchi; Maryam Daneshpazhoooh; Maede Rayati Damavandi; Zeinab Aryanian; Ali Akbar Amirzargar
Volume 10, Issue 1 , March 2013, , Pages 1-9
Abstract
Background: A common Human Leukocyte Antigen (HLA) class II allele, DQβ1*03:01, seems to be associated with Bullous pemphigoid (BP) in Caucasians whereas previous studies in other ethnic groups showed other HLA class II alleles as genetic predisposing factors for BP. Objective: To investigate the ...
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Background: A common Human Leukocyte Antigen (HLA) class II allele, DQβ1*03:01, seems to be associated with Bullous pemphigoid (BP) in Caucasians whereas previous studies in other ethnic groups showed other HLA class II alleles as genetic predisposing factors for BP. Objective: To investigate the association of HLA class II alleles and haplotypes with BP in Iranian population. Methods: Fifty patients with Bullous pemphigoid and 180 geographically matched, healthy individuals as control group enrolled into this study. HLA typing of class II (DR and DQ alleles) was carried out using polymerase chain reaction based on sequence-specific primers method. Results: Class II DQA1 and DQB1 typing showed a significantly higher frequency of HLA-DQA1*05:01 (45% vs. 33%, p=0.03), HLA-DQB1*03:01 (36% vs. 23.6%, p=0.02) and HLA-DQB1*04:01 (4% vs. 1.6%, p=0.04) in the BP patients compared with controls. For DRB1 allele frequencies, there were no significant disease associations. The frequency of DRB1*08:01/DQA1*05:01/DQB1*03:01 (3% vs. 0%, p=0.02) haplotype showed an increase among patients compared with controls. Conclusion: Our data suggest that Iranian patients with BP present the same genetic predisposition linked to HLA-DQB1*03:01 previously reported in Caucasians.
Esmaeil Sadroddiny; Jafar Ai; Kathleen Carroll; Trong Khoa Pham; Phillip Wright; Ashutosh Pathak; Birgit Helm
Volume 9, Issue 1 , March 2012, , Pages 1-31
Abstract
Background: Secretory proteins of IgE receptor activated mast cells and basophils play a pivotal role in the generation of immediate and long term immune responses in allergy and type I hypersensitivity. Objective: The present study aims to generate a 2-D map and profile of proteins secreted from a high ...
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Background: Secretory proteins of IgE receptor activated mast cells and basophils play a pivotal role in the generation of immediate and long term immune responses in allergy and type I hypersensitivity. Objective: The present study aims to generate a 2-D map and profile of proteins secreted from a high secretory variant of the rat basophilic leukemia cell line, RBL-2H3.1, which in view of the difficulty associated with gaining adequate numbers of pure primary mast cell and basophiles, represents an accepted model system for the study and standardization of the methodology to characterize the secretome of these cell types. Methods: A 2-D map of secretory proteins was generated by 2-D PAGE and a shotgun mass spectrometric approach carried out for protein identi fication. Results: Study resulted into identification of 299 proteins released from resting and IgE receptor activated RBL-2H3.1 cells after 90 s, 30 min and 3 h antigen challenge. Further sequence analysis identified ~53% of total proteins as secretory proteins which could be attributed to classical and non-classical secretory pathways. Additionally, functional classification of classic secretory proteins verified the presence of proteins belonged to cytokines, receptors, membrane proteins, lysosomal proteins and proteins associated with specific sub-cellular localizations such as endoplasmic reticulum, mitochondria, nucleus, cytoplasm and ribosome. According to this data the presence of some secretory proteins such as cytokines (e.g. MCP-2, PF-4, CSF-1 and TGF-β1) are all subject to Ag challenge which may point to their importance toward pathogenesis in allergic diseases. Conclusion: In view of both a beneficial and adverse role of mast cell mediators in health and disease, an identification of temporal changes in the secretory pattern may form the basis for future tailor made intervention strategies that may enable us to harvest the therapeutic potential inherent in mast cell exocytosis while inhibiting/attenuating negative outcomes.
Alireza Andalib; Hassan Doulabi; Mohammadreza Najafi; Mehdi Tazhibi
Volume 8, Issue 1 , March 2011, , Pages 1-10
Abstract
Background: Th1 cells preferentially express CXCR3, CCR5 and CCR6, while CCR3 and CCR4 are predominantly expressed by Th2 cell subsets. Multiple Sclerosis (MS) is a Th1 cell-dependant chronic inflammatory disease of the central nervous system, and immunomudolatory cytokines could alter the chemokine ...
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Background: Th1 cells preferentially express CXCR3, CCR5 and CCR6, while CCR3 and CCR4 are predominantly expressed by Th2 cell subsets. Multiple Sclerosis (MS) is a Th1 cell-dependant chronic inflammatory disease of the central nervous system, and immunomudolatory cytokines could alter the chemokine expression pattern of these lymphocyte subsets. Objective: This study was performed to measure chemokine receptor expression on CD4 T cells for evaluation of Th1/Th2 dominantly in IFN-β treated patients. Methods: flowcytometry was used to detect chemokine receptor expression on CD4 T cell population in PBMCs obtained from MS and healthy control groups. Twenty six MS patients participated in this study before and after IFN-β therapy and the same number of healthy individuals were included. Results: The percentage of lymphocytes was 41.28% ± 10.30 in the blood of MS group compared with 36.88% ± 5.51% in the control group (p=0.017). The CD4+CXCR3+ cells were 18.86% ± 8.46% in healthy group, 30.78% ± 9.8% in pre-treated MS patients and 21.06% ± 9.23% in posttreated group (p<0.001). The CD4+CCR4+ cell subsets were 27.35% ± 10.15% in healthy group; 28.17% ± 8.9% in pre-treated group and 34.20% ± 8.96% in the post- IFN-β treatment group. The subset of CD4+CCR4+ was found to be dominant after IFN- β therapy in comparison with the control group (p<0.001). CD4+CCR5+ percentage was 1.24% ± 0.92% in the healthy people, 1.23% ± 0.71% in the MS patients and 0.76% ± 0.49% in post-treatment status (p=0.003). CD4+CCR3+ cell subsets were 0.62% ± 0.67% in control group, 0.28% ± 0.26% in the MS patients (p=0.022) and 0.39% ± 0.54% in IFN-β treated patients (p=0.334). An association was found for CXCR3 expression in pre- and post- treatment status (r=0.840, p<0.001) as well as for CCR4+ expression (r=0.712, p<0.001) in the same groups. The Th1 response was dominant in pre-treatment states, and then it shifted to a Th2 dominant state after IFN-β treatment. Conclusion: We suggest that the chemokine receptor expression of Th1/Th2 cell subsets could be used for monitoring and the evaluation of the MS disease status.
Alireza Zamani; Jalil Tavakkol Afshari; Mohammad Yousef Alikhani
Volume 3, Issue 1 , March 2006, , Pages 1-8
Abstract
Background: IFN-g is mostly secreted by activated CD4+ , CD8+ T cells and NK cells. This cytokine has immunomodulatory, anti-cancer and anti-microbial effects and is important for prophylaxis, diagnosis and treatment of chronic infections and cancers. Objective: The purpose of this study was to clone ...
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Background: IFN-g is mostly secreted by activated CD4+ , CD8+ T cells and NK cells. This cytokine has immunomodulatory, anti-cancer and anti-microbial effects and is important for prophylaxis, diagnosis and treatment of chronic infections and cancers. Objective: The purpose of this study was to clone the full cDNA of human IFN-g and express it in CHO cell line. Methods: Lymphocytes from a healthy individual were isolated and activated by phytohaemagglutinin (PHA) in vitro. After 4 hours, total RNA extracted and first cDNA strand was synthesized. cDNA was amplified with primers containing EcoRI and NotI sites. The amplified fragment and the PcDNA3.1 vector were cut by EcoRI and NotI and ligated. The construct (pcDNA3.1-IFN-γ) was transferred into E.coli (DH5α strain) using CaCl2 method and selected by plating on a medium containing ampicillin. The construct sequence was confirmed by PCR and sequence analysis. Construct expression was achieved by performing a calcium phosphate-mediated transfection into CHO cells and followed by selection of stable drug (G418) resistant clones by limiting dilution assay (LDA). The IFN-γ production by transfected CHO cells was measured using ELISA technique. Results and Conclusion: Out of 33 grown transformed bacterial colonies, only 6 had the entire sequences of the inserted fragment and one of them was used for the transfection experiment. Out of 768 wells, 5 clones produced more than 100 ng/ml/106 cells of IFN-γ. Among the 5 clones, one with the maximum production of INF-g (143 ng/ml/106 cells) was selected and used for propagation.
Mohammad Fereidouni; Farhzad Jabbari Azad; Mahmoud Mahmoudi; Abdolreza Varasteh; Reza Farid Hosseini
Volume 7, Issue 1 , March 2010, , Pages 1-7
Abstract
Background: Invariant natural killer cells (iNKT) are an important immunoregulatory T cell subset. Currently several flow cytometry-based approaches exist for the identifi-cation of iNKT cells, which rely on using the 6B11 monoclonal antibody or a combina-tion of anti-Vα24 and anti-Vβ11 antibodies. ...
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Background: Invariant natural killer cells (iNKT) are an important immunoregulatory T cell subset. Currently several flow cytometry-based approaches exist for the identifi-cation of iNKT cells, which rely on using the 6B11 monoclonal antibody or a combina-tion of anti-Vα24 and anti-Vβ11 antibodies. Objective: The aim of this study was to compare the ability of two flow cytometry-based methods for detecting the frequency of circulating iNKT cells. Methods: The frequency of iNKT cells was detected in the pe-ripheral blood of 37 healthy adult donors by flow cytometry using the 6B11 antibody or a combination of anti-Vα24 and anti-Vβ11 antibodies. Results: The frequency of iNKT cells detected by 6B11 antibody or by combination of anti-Vα24 and anti-Vβ11 anti-bodies was significantly different (0.54% vs. 0.31%, respectively, p<0.001) but the val-ues were highly correlated (Spearman r = 0.742, p<0.0001). Conclusion: The results of this study indicate that different combinations of mAbs detect different frequencies of peripheral blood iNKT cells and a consensus in the field needs to be established to al-low better assessment of iNKT-related studies and suggest using different methods for accurate identification of iNKT cells.
Zohreh Babaloo; Farhad Babaie; Mehdi Farhoodi; Mohammadreza Aliparasti; Behzad Baradaran; Shohreh Almasi; Ahmad Hosseini
Volume 7, Issue 4 , December 2010, , Pages 1-1
Abstract
Bakground: Multiple sclerosis (MS) is a CD4+ T cell-mediated autoimmune disease affecting the central nervous system (CNS). It was previously believed that Th1 cells were pathogenic T cells in experimental autoimmune encephalomyelitis (EAE). However, the functional role of Th1 cells in EAE has been reconsidered ...
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Bakground: Multiple sclerosis (MS) is a CD4+ T cell-mediated autoimmune disease affecting the central nervous system (CNS). It was previously believed that Th1 cells were pathogenic T cells in experimental autoimmune encephalomyelitis (EAE). However, the functional role of Th1 cells in EAE has been reconsidered upon the discovery of IL-17- producing T cells which are consider as dominant effectors for inducing autoimmune tissue inflammation. Objective: The objective of this study was to assess the role of IL-17A and IL-17F in MS pathogenesis. Methods: We evaluated mRNA expression of IL-17A and IL-17F in thirty-five Iranian patients with relapsing–remitting MS (RRMS) and twenty-five healthy controls by Quantitative Real Time PCR. Results: The results of this study showed a twenty-fold increase in the expression of IL-17A mRNA in MS patients compared to the control group (p < 0.0001 ). IL-17F mRNA expression in MS patients was thirty three-times greater than control group (p = 0.0008). IL-17A mRNA expression in periphery was positively correlated with expression of IL-17F transcripts in MS patients and controls (p < 0.01 and p < 0.05, respectively). Conclusion: These results indicate the critical role of Th17- mediated cytokines in development of MS which classically has been considered as a Th1-mediated disorder. The results of this study showed, for the first time, the importance of IL-17F in MS immunopathogenesis.
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.
Kayhan T Nouri-Aria
Volume 5, Issue 1 , March 2008, , Pages 1-24
Abstract
The efficacy of allergen immunotherapy for the treatment of allergic rhinoconjunctivitis with or without seasonal bronchial asthma and anaphylaxis caused by the sting of the hymenoptera class of insects has been clearly demonstrated in numerous well-designed, placebo-controlled trials. Immunotherapy ...
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The efficacy of allergen immunotherapy for the treatment of allergic rhinoconjunctivitis with or without seasonal bronchial asthma and anaphylaxis caused by the sting of the hymenoptera class of insects has been clearly demonstrated in numerous well-designed, placebo-controlled trials. Immunotherapy whether by subcutaneous injection of allergen extract or by oral/sublingual routes modifies peripheral and mucosal TH2 responses in favour of TH1 responses and augments IL-10 synthesis by TRegs both locally and by pe-ripheral T cells. Recent researches into the cellular and molecular basis of allergic reac-tions have advanced our understanding of the mechanisms involved in allergic diseases. They have also helped the development of innovative approaches that are likely to fur-ther improve the control of allergic responses in the future. Novel approaches to immu-notherapy that are currently being explored include the use of peptide-based allergen preparations, which do not bind IgE and therefore do not activate mast cells, but reduce both TH1 and TH2-cytokine synthesis, while increasing levels of IL-10. Alternative strategies include the use of adjuvants, such as nucleotide immunostimulatory se-quences derived from bacteria CpG or monophosphoryl lipid A that potentiate TH1 re-sponses. Blocking the effects of IgE using anti-IgE such as omalizumab, a recombinant humanized monoclonal antibody that selectively binds to IgE, has been shown to be a useful strategy in the treatment of allergic asthma and rhinitis. The combination of anti-IgE-monoclonal antibody omalizumab with allergen immunotherapy has proved benefi-cial for the treatment of allergic diseases, offering improved efficacy, limited adverse effects, and potential immune-modifying effects. This combination may also accelerate the rapidity by which immunotherapy induces TReg cells. If allergic diseases are due to a lack of allergen-specific TReg cells, then effective therapies should target the induction and the development of TReg cells producing cytokines such as IL-10.
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.
Noha Mohamed El Husseiny; Walaa Abd El Fattah Attya Elkak; Mervat Said El Ansary; Engy Mohamed Abd El Aziz El Khateeb; Mervat Wagih Mattar; Doaa Mohamed El Demerdash
Volume 14, Issue 1 , March 2017, , Pages 1-12
Abstract
Background: Generation of monocyte-derived dendritic cells (MDDC) is induced in the presence of GM-CSF and IL-4, and a maturation stimulus is added to the monocyte culture to obtain mature Dendritic Cells (DCs) suitable for therapy. TNF-α is the most common cytokine used for activating DCs and ...
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Background: Generation of monocyte-derived dendritic cells (MDDC) is induced in the presence of GM-CSF and IL-4, and a maturation stimulus is added to the monocyte culture to obtain mature Dendritic Cells (DCs) suitable for therapy. TNF-α is the most common cytokine used for activating DCs and generating mature MDDC either alone or in combination with other cytokines. Objective: To compare effects of traditional cytokine cocktail (TNF-α + IL-1β) versus TLR4-agonist monophosphoryl lipid A on the viability, phenotype, cytokine profile and functionality of MDDC. Methods: The study included 32 individuals; twenty Acute Myeloid Leukaemia (AML) cases in complete remission and 12 healthy volunteers. They were divided into 3 groups: Group 1: control group: 12 subjects to measure the baseline levels of all markers in the monocytic preparation; Group 2: cytokine cocktail (TNF-α) group, which included 10 AML subjects; Group 3: MPLA group which included 10 AML subjects. Results: TNF-α group showed higher expression of CD83 than MPLA group indicating higher capacity to induce DC maturation but both were similar in CD86, CCR7 and IL-10 expression. Preparation of dendritic cells from AML cases in remission and loading them with tumor peptides was successful. Conclusion: The effect of MPLA in DC maturation is comparable with traditional DC maturation cocktail.
Sait Karaman; Semiha Bahçeci Erdem; Nesrin Gülez; Ferah Genel
Volume 15, Issue 1 , March 2018, , Pages 1-13
Abstract
Background: Patients with unclassified hypogammaglobulinemia (UCH) constitute a diagnostic and therapeutic dilemma, because information concerning the clinical and immunological characteristics of these patients is insufficient. Objective: To evaluate B-cell subsets in cases with UCH and common variable ...
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Background: Patients with unclassified hypogammaglobulinemia (UCH) constitute a diagnostic and therapeutic dilemma, because information concerning the clinical and immunological characteristics of these patients is insufficient. Objective: To evaluate B-cell subsets in cases with UCH and common variable immunodeficiency (CVID) and their association with treatment requirement in UCH patients. Methods: The study included 41 UCH, 25 CVID, and 36 healthy individuals between the ages of 4-18 years. Results: The absolute count of total memory and switched memory B-cells were lower in the CVID cases in comparison to the control group. Additionally, the absolute count of marginal zone-like B cells in the 4-10 year age group, and the absolute count of switched plasmablasts in the 10-18 year age group were lower in CVID cases when compared to both the control and UCH groups. The UCH group was categorized based on IVIG replacement therapy. Therefore, the percentage of switched memory B cells was significantly lower in the IVIG-receiving group (10.6% ± 3.10%) compared to the control group (14.0% ± 5.60%). However, there was no significant difference between the IVIG-receiving group and the CVID group. Regarding the comparison of the non-IVIG replacement group and the CVID group, the absolute count of total memory B cells, marginal zone-like B cells, and switched memory B cells were significantly higher in the UCH group. Conclusion: B-lymphocyte subsets in UCH cases that did not require IVIG replacement were similar to the control group. On the other hand, the percentage of switched memory B-cells in the UCH cases that required IVIG replacement was not different from that of the CVID cases.
Suqian Wu; Wentao Wang; Qihua Le
Hongyan Xu; Yueqing Yang; Qianhong Wu; Yan Zhang
Abstract
Background: Patient immune status might be indicative of the variance in bacterial genetics in drug-resistant tuberculous pleuritis and could be used for predicting the risk of multi-drug resistant tuberculous pleuritis (MDR-TB). Objective: To determine the significance of Th2/Th1 ratio and concentration ...
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Background: Patient immune status might be indicative of the variance in bacterial genetics in drug-resistant tuberculous pleuritis and could be used for predicting the risk of multi-drug resistant tuberculous pleuritis (MDR-TB). Objective: To determine the significance of Th2/Th1 ratio and concentration of PD-L1 in the pleural effusions for prediction of MDR-TB. Methods: We measured the ratio of Th2 to Th1 T cells from pleural effusions in 373 tuberculous pleuritis patients. We also measured the concentration of programmed death ligand-1 (PD-L1) in the pleural effusions of these patients. Afterwards, we determined the optimal cut-off value for predicting the occurrence of multi-drug resistant tuberculous based on the Youden index, diagnostic evaluation test, and receiver operation curve. Multiple logistic analysis was employed to identify the independent risk factors for MDR-TB occurrence. Results: The area under the curve (AUC) of the Th2 to Th1 ratio was 0.66 and the concentration of PD-L1 was 0.71. Based on the combined detection of PD-L1 concentration in pleural effusion and the Th2 to Th1 ratio, our AUC was 0.81 and had a specificity of 0.92. Only a combined detection was able to identify patients developing multidrug-resistant tuberculosis. Multiple logistic analysis showed that a high concentration of PD-L1 and a high Th2 to Th1 T ratio in pleural effusions were indicative of an immunocompromised status. Therefore, these measurements might be independent risk factors for the occurrence of multidrug-resistant tuberculous. Conclusion: Evaluation of immune status based on PD-L1 pleural concentration and Th2 to Th1 ratio might predict the risk of MDR-TB occurrence.
Helmout Modjtahedi
Volume 2, Issue 1 , March 2005, , Pages 3-20
Abstract
Despite the major advances in conventional forms of treatment (i.e. surgical techniques, radiotherapy and chemotherapy) and improved survival rates, cancer is still the second leading cause of death in developing countries. One major limitation of cytotoxic drugs and radiation in the treatment of cancer ...
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Despite the major advances in conventional forms of treatment (i.e. surgical techniques, radiotherapy and chemotherapy) and improved survival rates, cancer is still the second leading cause of death in developing countries. One major limitation of cytotoxic drugs and radiation in the treatment of cancer patients is their inability to discriminate between malignant and normal tissues. This in turn prevents the delivery of the optimal (therapeutic) dose of such agents to malignant tissues for their eradication. With the advent of hybridoma technology in 1975, it has been possible for the first time to produce large amounts of an antibody (i.e. monoclonal antibody) against any antigens of interest. Since each antibody is highly specific for a particular antigen, this typical feature of the antibodies has resulted in their widespread use in diagnostic kits, medical research (e.g. to unravel the function of the antigen in physiological and pathological conditions), and more recently, for the management of a wide range of human diseases such as autoimmune disease and human cancers. Thanks to recent advances in genetic engineering, the immunogenicity of rodent antibodies was reduced by producing the chimeric or humanized version of such antibodies or by developing the fully human antibodies. In other instances, as intact antibodies are too large for rapid penetration into solid tumours, it has been possible to develop a smaller fragment of such antibodies (e.g. Fab, scFv, VHH) with greater potential for use in cancer imaging and therapy. Depending on the target antigens and the antibody format, monoclonal antibodies can induce their anti-tumour activities by several mechanisms including activation of the host effector cells. To date, several mAbs have been approved for management of human cancers including: anti-EGFR antibody cetuximab and anti-VEGF antibody bevacizumab for treatment of metastatic colorectal cancer, anti-HER-2 antibody trastuzumab for metastatic breast cancer, anti-CD20 antibodies rituximab and ibritumomab tituxetan for non-Hodgkin lymphoma, anti- CD52 antibody alemeutumab for chronic lymphocytic leukaemia, and anti-CD33 antibody gemutuzumab ozogamicin for the treatment of acute myeloid leukaemia patients. Monoclonal antibodies currently account for about 30% of all new drugs in development, with more than 500 antibodies at different stages of clinical trials worldwide. In this review, the characteristic features of some of the therapeutic antibodies and the antigens recognised by such antibodies will be discussed as well as several challenges that need to be addressed in order to facilitate their widespread use as “magic bullets” in the management of human diseases and in particular human cancers.
Mojtaba Zarei
Volume 1, Issue 1 , June 2004, , Pages 6-25
Abstract
Clinical neurology has been traditionally considered as an academic speciality in which the specialist regurgitates his/her knowledge of neurology without being able to do much for the patient. This attitude is no longer acceptable. Surge of information and discoveries in neurosciences within the last ...
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Clinical neurology has been traditionally considered as an academic speciality in which the specialist regurgitates his/her knowledge of neurology without being able to do much for the patient. This attitude is no longer acceptable. Surge of information and discoveries in neurosciences within the last two decades translated into therapeutic interventions which is literally life saving in some occasions. Neuroimmunology, without a doubt, has been in the forefront of such discoveries. Just a few decades ago immunology of the nervous system was of little interest because brain was thought to be an immunologically “privileged” organ i.e. inaccessible to cellular and humeral immunity. Today, however, clinical neurologists deal with neurological problem with immunological basis on a daily basis. This article tries to review such diseases and their current therapeutic strategy proceeded by an introduction to CNS immunity. Multiple sclerosis, as one of the most common CNS disease with immunological basis, has been given more attention because of the growing number of affected people in Iran.
Gholamhossein Hassanshahi; Mohammad Kazemi Arababadi; Alan James Dickson
Volume 3, Issue 2 , June 2006, , Pages 54-60
Abstract
Background: It is now well established that several environmental stress factors cause activation of p38 MAP kinase and JNK in various cell types to produce chemokines. Objective: To investigate the expression of CXC chemokines Gro/KC and SDF- 1a in rat's H4 hepatoma cells in response to heat shock, ...
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Background: It is now well established that several environmental stress factors cause activation of p38 MAP kinase and JNK in various cell types to produce chemokines. Objective: To investigate the expression of CXC chemokines Gro/KC and SDF- 1a in rat's H4 hepatoma cells in response to heat shock, hyperosmolarity and oxidative stress. Methods: Hepatoma cells were maintained in MEM medium. Cells were subjected to different stresses [(H2O2 0.15% (w/v), manitol and NaCl (160 mM) and heat shock (42 °C for 20 minutes)]. Cells were harvested and RNA was extracted, purified and the CXC chemokine Gro/KC and SDF-1a expression was analysed by RT-PCR. cDNA was separated by gel electrophoresis on a 1% (w/v) agarose gel and visualized under a UV transilluminator. Results: There was detectable but low expression of both SDF-1a and Gro/KC in H4 hepatoma cells. Heat shock failed to induce expression of SDF-1a and Gro/KC in H4 hepatoma cells of rat. Hyperosmolarity also did not stimulate SDF-1a and Gro/KC expression. In this study we have also shown that oxidative stress did not induce expression of SDF-1a and Gro/KC. Overall, although detection is possible but regulatory responses were not observed in H4 hepatoma cells. Conclusion: Several known injurious conditions cause recruitment of macrophages, neutrophils and other immune cells to the liver. Immune cells are recruited to the hepatic vasculature following local liver injury and subsequent chemokine production. Our results demonstrated that failure to produce chemokines by hepatoma cells may be a way to escape from mechanism of immune surveillance.
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.
Raja Rajalingam
Volume 4, Issue 2 , June 2007, , Pages 61-78
Abstract
Natural killer (NK) cells are a subset of lymphocytes which play a crucial role in early innate immune response against infection and tumor transformation. Furthermore, they secrete interferon-γ (IFN-γ) and tumor necrosis factor (TNF) prompting adaptive immu-nity. NK cells distinguish the ...
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Natural killer (NK) cells are a subset of lymphocytes which play a crucial role in early innate immune response against infection and tumor transformation. Furthermore, they secrete interferon-γ (IFN-γ) and tumor necrosis factor (TNF) prompting adaptive immu-nity. NK cells distinguish the unhealthy cells from the healthy ones through an array of cell-surface receptors. Human NK cells use inhibitory and activating killer cell Ig-like receptors (KIR) as primary probe to discriminate between healthy and unhealthy cells. The inhibitory KIRs recognize HLA class I molecules and trigger signals that stop NK killing. The activating KIRs are believed to recognize the determinants associated with infections and tumors, and trigger signals that activate NK killing. Therefore, the effec-tor function of a given NK cell depends upon the receptors that it expresses and ligands that it recognizes on the targets. Genes encoding KIRs and HLA ligands are located on different chromosomes, and vary in number and type. The independent segregation of KIR and HLA genes results in variable KIR-HLA combinations in individuals, which may determine the individual’s immunity and susceptibility to disease.
Bahareh Abd Nikfarjam; Massoumeh Ebtekar; Farzaneh Sabouni; Zahra Pourpak; Maryam Kheirandish
Volume 10, Issue 2 , June 2013, , Pages 62-69
Abstract
Background: Astrocytes, which comprise ~90% of overall brain mass, are involved in brain immunity. These cells represent the non-professional class of CNS-resident APCs and may promote or inhibit CNS inflammation depending on the cytokines they secrete. IL-10 family of cytokines and their receptors, ...
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Background: Astrocytes, which comprise ~90% of overall brain mass, are involved in brain immunity. These cells represent the non-professional class of CNS-resident APCs and may promote or inhibit CNS inflammation depending on the cytokines they secrete. IL-10 family of cytokines and their receptors, IL-20R1 and IL-20R2, may have a role in shifting astrocytes to a neuroprotective or neurodegenerative function. Objective: To address the expression of IL-20R1 and IL-20R2 cytokine receptors in astrocytes and brain cortex of C57BL/6 mice. Methods: We investigated the expression of IL-20R1 and IL-20R2 in C57BL/6 mice astroglial cells and brain cortex in response to lipopolysaccharide (LPS), using reverse-transcription polymerase chain reaction (RTPCR) method. Results: Astrocytes were able to express IL-20R1 and IL-20R2 mRNA not only in response to LPS stimulation but also in the absence of LPS. Furthermore, we found the expression of IL-20R1 and IL-20R2 mRNA in the cortex of adult C57BL/6 mice. Conclusions: IL-20R1 and IL-20R2 are constitutively expressed in the brain. Since most neuropathological processes involve astrocytes and inflammatory cytokines, these findings have important implications for future therapeutic strategies.
Volume 7, Issue 2 , June 2010, , Pages 64-73
Hossein Rezvan; Ali Khodadadi; Selman Ali
Volume 11, Issue 2 , June 2014, , Pages 65-73
Abstract
Background: Leishmania is a pathogenic parasite which infects mononuclear cells in vertebrate hosts. Different strategies have been taken to develop immunity against Leishmania . DCs loaded with immunogenic antigen have resulted in different levels of Th1-type immune response and cytotoxic T lymphocytes ...
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Background: Leishmania is a pathogenic parasite which infects mononuclear cells in vertebrate hosts. Different strategies have been taken to develop immunity against Leishmania . DCs loaded with immunogenic antigen have resulted in different levels of Th1-type immune response and cytotoxic T lymphocytes (CTL) activity. Objective: To evaluate the potency of DCs primed with soluble Leishmania mexicana antigens (SLA) in developing CTL activity. Methods: DCs were loaded with SLA and injected to Balb/c mice. After two weeks the mice were sacrificed and their splenocytes were used as effector cells in a standard 4-hour cytotoxicity assay against DCs transfected with pcDNA3 containing L. mexicana gp63 gene. Results: Immunization of Balb/c mice with DCs loaded with SLA resulted in high levels of CTL activity against DCs transfected with pcDNA3 containing L. mexicana gp63 gene. Conclusions: The results indicate a high potency for DCs primed with Leishmania antigens in inducing CTL activity, which can be used for developing an immunogenic vaccine against Leishmania.
Zahra Meshkat; Hoorieh Soleimanjahi; Hessam Mirshahabi; Mojtaba Meshkat; Maryam Kheiandish; Zuhair Mohammad Hassan
Volume 8, Issue 2 , June 2011, , Pages 65-75
Abstract
Background: Vaccines capable of controlling tumor virus based infections are found difficult to develop due to the consistence latent infection in the host. DNA vaccines are attractive tools for the development of HPV vaccines and inducing antigen-specific immunity owing to the stability, simplicity ...
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Background: Vaccines capable of controlling tumor virus based infections are found difficult to develop due to the consistence latent infection in the host. DNA vaccines are attractive tools for the development of HPV vaccines and inducing antigen-specific immunity owing to the stability, simplicity of delivery, safety and cost effectiveness. However, there is a need to increase their potency by procedures such as using HSP70 gene as an adjuvant. Objective: To evaluate a DNA vaccine containing HPV16 truncated E7 C-terminal cytotoxic T-lymphocyte epitopes linked to HSP70 gene (HSP70-tE7) in an animal model. Methods: Mice were immunized with the plasmid DNA after pre-treatment with cardiotoxin. The splenocytes of immunized mice were then tested for CTL activity by detecting the apoptosis and necrosis in target cells, cytokine production by ELISA, CD4 and CD8 frequencies by flow cytometry, and lymphocyte stimulation by MTT assay. Results: The recombinant expression vector was able to elicit immune responses close to that of full length E7 complete gene. Although the use of a small part of a target antigen can induce immune responses equivalent to the full length antigen, it fails to elicit statistically significant stronger immune responses when fused with HSP70 compared to the complete E7 gene alone. Conclusion: The potent immunogenicity of HPV16 E7 was preserved in the HSP70-tE7 vaccine and may represent a target of choice for the therapeutic vaccination strategies. However, to improve the immunogenicity polytope DNA vaccines which elicit multiple effector and memory CTL responses should be considered in future studies of DNAbased cancer vaccines.