فهرست مطالب
Iranian journal of immunology
Volume:12 Issue: 4, Autumn 2015
- تاریخ انتشار: 1394/10/20
- تعداد عناوین: 8
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Page 226BackgroundDifferentiation, migratory properties and availability of Mesenchymal Stromal Cells (MSC) have become an important part of biomedical research. However, the functional heterogeneity of cells derived from different tissues has hampered providing definitive phenotypic markers for these cells.ObjectiveTo characterize and compare the phenotype and cytokines of adipose derived MSCs (AD-MSCs) and tumoral-MSCs (TMSCs) isolated from mammary tumors of BALB/c mice.MethodsImmunophenotyping and in vitro differentiation tests were used for MSC characterization. Cytokine and enzyme profiles were assessed using ELISA and Real-time PCR, respectively.ResultsT-MSCs expressed significantly higher levels of HLA-DR (p=0.04). Higher levels of PGE2 and COX-2 enzyme were also observed in T-MSCs (p=0.07 and p=0.00, respectively). Additionally, T-MSCs expressed higher levels of iNOS and MMP9 (p=0.01 and p=0.01, respectively). T-MSCs were also able to induce higher levels of proliferation and migration of HUVEC endothelial cells in wound scratch assay compared to AD-MSCs (p=0.015).ConclusionFunctional differences showed by the surface markers of MSCs, cytokine and enzyme production indicate the effect of different microenvironments on MSCs phenotype and function.Keywords: Adipose, Derived Mesenchymal Stromal Cells, Breast Cancer, Immunomodulatory Properties, Tumoral, MSCs
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Page 240BackgroundType 1 diabetes (T1D) is a T cell mediated autoimmune disease targeting the insulin-producing β cells within pancreatic islets. Autoimmune diseases may develop as a consequence of altered balance between regulatory (Tregs) and autoreactive T cells.ObjectivesTo evaluate Treg cells frequency and suppressive function in the peripheral blood of newly diagnosed T1D patients in comparison with healthy controls.MethodsFifteen new cases of T1D patients and 15 age- and sex- matched healthy controls were recruited to this study. Their peripheral blood mononuclear cells (PBMCs) were isolated and CD4+CD25+FoxP3+CD127-/low Treg cells were studied by flowcytometry technique. Thereafter, Tregs were isolated by Magnetic-Activated Cell Separation (MACS) technology and by using CFSE (carboxyfluorescein succinimidyl ester) dilution assay, their suppressive activity was evaluated in the coculture of CD4+CD25- T responder cells with Treg cells.ResultsThe percentage of CD4+CD25+FoxP3+CD127-/low Tregs did not differ between T1D patients and healthy controls but the MFI (mean fluorescence intensity) of transcription factor FoxP3 (forkhead box protein P3) was significantly decreased in T1D patients (20.03 ± 1.4 vs. 31.33 ± 2.95, p=0.0017). Moreover, the suppressive function of CD4+CD25+CD127-/low Treg cells was significantly diminished in T1D patients in comparison with control group (35.16 ± 4.93% vs. 60.45 ± 5.26%, respectively, p=0.0015).ConclusionPresent study indicates an impaired immune regulation among T1D patients, characterized by defects in suppressive function and expression of FoxP3 in Treg cells without any significant decrease in their frequency in peripheral blood. Aghili B, et al. Iran J Immunol. 2015; 12(4):240-251.Keywords: Regulatory T Cells (Tregs)_Suppressive Function_Type 1 Diabetes (T1D
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Page 252BackgroundRecurrent miscarriage (RM) affects 2-5% of pregnant women. Paternal lymphocyte immunotherapy is a common treatment for RM patients but the outcome has not been consistent. Therefore, combined therapy with other immunosuppressive drugs such as 1a, 25-dihydroxy-vitamin-D3 (vitamin D3) may improve the outcome.ObjectivesTo investigate the effect of vitamin D3 on the balance of two essential T cells subsets, T helper (Th) 17 and T regulatory (Treg) cells, which regulate tolerance.MethodsThe expression levels of CD4 and forkhead box protein 3 (FOXP3) in Treg cells, and the expression levels of CD4 and IL-17 in Th17 cells, were evaluated pre- and 3 months postimmunotherapy in RM patients treated with a combination of paternal lymphocytes and vitamin D3 compared with RM patients receiving lymphocyte immunotherapy alone.ResultsVitamin D3 therapy decreased the frequency of Th17 cells in addition to reducing the Th17/Treg ratio in peripheral blood of RM patients compared with the control group (p<0.05).ConclusionConsidering that RM patients have a higher Th17/Treg ratio in peripheral blood, vitamin D3 may be a candidate therapeutic approach in this disease. Rafiee M, et al. Iran J Immunol. 2015; 12(4):252-262.Keywords: Paternal Lymphocyte Therapy_Recurrent Miscarriage_Regulatory T Cell_T Helper 17_Vitamin D3
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Page 263BackgroundH2-EB1 molecule which is the homolog of Human HLA-DRB1 is proposed to be associated with allergic rhinitis (AR). Construction of H2-Eb1 knockout animal models provides a tool to elucidate the role of H2-EB1 and AR pathogenesis.ObjectiveTo establish the H2-Eb1 knockout model and investigate the H2-EB1 functions in H2-Eb1 knockout mice as a model of AR.MethodsThe Cre/LoxP system and ES gene knockout technology were applied to create heterozygous H2-Eb1 (+/-) knockout mice and their offspring of knockout homozygous(-/-), heterozygous (+/-) and wild type (+/+) H2-Eb1 mice. After identification, offspring of heterozygous (+/-) and homozygous (-/-) H2-Eb1 knockout mice were randomly selected to establish AR models to demonstrate the role of H2-Eb1 in AR pathogenesis.ResultsThe H2-Eb1 knockout mice model was successfully established. The reproduction and feeding of the homozygous (-/-) H2-Eb1 knockout mice were successful. Compared with the control group, the serum OVA-IgE and IL-4 levels significantly increased, while IFN-γ levels significantly dropped (p<0.05) in the experimental groups. For the two experimental groups, the homozygous (-/-) mice group had lower serum OVA-IgE and IL-4 levels, and higher IFN-γ levels than their heterozygous (+/-) counterparts (p<0.05), concomitant with slighter allergic symptoms (gentle behavior and less eosinophils in nasal mucosa).ConclusionOur study demonstrated that knockout of H2-Eb1 gene could alleviate mouse AR Symptoms, indicating H2-Eb1 may play an important role in regulating Th1/Th2 balance during the pathogenesis of AR. Li L,et al. Iran J Immunol. 2015; 12(3):263-273.Keywords: H2, Eb1, Allergic Rhinitis, Knockout, Th1, Th2
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Page 274BackgroundCationic immune stimulating complexes (PLUSCOMs) are particulate antigen delivery systems. PLUSCOMs consist of cationic immunostimulatory complexes (ISCOMs) derivatives and are able to elicit in vivo T cell responses against an antigen.ObjectiveTo evaluate the effects of PLUSCOMs containing Leishmania major antigens (SLA) on the type of immune response generated in the murine model of leishmaniasis.MethodsPLUSCOMs consisting of 1, 2-dioleoyl-3-trimethylammonium-propane (DOTAP) were used as antigen delivery system/immunoadjuvants for soluble SLA. BALB/c mice were immunized subcutaneously, three times in 2-week intervals. Footpads swellings at the site of challenge and parasite loads were assessed as a measure of protection. The immune responses were also evaluated by determination of IgG subclasses and the level of IFN-γ and IL-4 in cultured splenocytes.ResultsThere was no significant difference (p<0.05) between the sizes of lesions in mice immunized with different formulations. Also, there was no significant difference in the number of parasites in the footpad or spleen of all groups compared with the control group. The highest level of IFN-γ secretion was observed in the splenocytes of mice immunized with PLUSCOM/SLA (p<0.001) and lower amounts of IL-4 was observed in PLUSCOM group (p<0.001) as compared to negative control.ConclusionOur results indicated that SLA in different formulations generated an immune response with mixed Th1/Th2 response that was not protective enough despite the activation of CD4+ T cells with secreting IFN-γ in groups which received PLUSCOM with antigen. Mehravaran A, et al. Iran J Immunol. 2015; 12(4):247-287.Keywords: Leishmania major, Nanoparticle, PLUSCOM, Vaccine
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Page 288BackgroundIL-17/IL-23 axis plays an important role in the pathogenesis of several autoimmune diseases such as experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis (MS). The immunomodulatory properties of ginger are reported in previous studies.ObjectiveTo evaluate the effects of ginger extract on the expression of IL-17 and IL-23 in a model of EAE.MethodsEAE was induced in C57BL/6 mice by immunization with myelin oligodendroglial glycoprotein and then treated with PBS or ginger extracts, from day +3 to +30. At day 31, mice were scarificed and the expression of IL-17 and IL-23 mRNA in spinal cord were determined by using real time-PCR. The serum levels of cytokines were measured by ELISA.ResultsThe mRNA expression of IL-17, IL-23 P19 and IL-23 P40 in CNS and serum levels of IL-17 and IL-23 were significantly higher in PBS-treated EAE mice than non-EAE group (p<0.003, p<0.001, p<0.001, p<0.05 and p<0.01, respectively). In 200 mg/kg ginger-treated EAE mice the mRNA expression of IL-17, P19 and P40 in CNS and serum IL-23 levels were significantly decreased as compared to PBS-treated EAE mice (p<0.05, p<0.001, p<0.001 and p<0.05, respectively). Moreover, 300 mg/kg ginger-treated EAE group had significantly lower expression of IL17, P19 and P40 in CNS and lower serum IL-17 and IL-23 levels than PBS-treated EAE group (p<0.02, p<0.001, p<0.001, p<0.03 and p<0.004, respectively).ConclusionGinger extract reduces the expression of IL-17 and IL-23 in EAE mice. The therapeutic potential of ginger for treatment of MS could be considered in further studies. Jafarzadeh A, et al. Iran J Immunol. 2015; 12(4):288-301.Keywords: Experimental Autoimmune Encephalomyelitis, Ginger, IL, 17, IL, 23
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Page 302BackgroundRuptured cerebral aneurysms (ICAs) are the most common non-traumatic cause of subarachnoid hemorrhage (SAH) that is associated with life threatening complications such as Vasospasm, Infarction, and Hydrocephalus (HCP). The active participation of macrophage/monocyte-mediated inflammatory response in the pathogenesis of cerebral aneurysm as labeled with Monocyte Chemoattractant Protein-1 (MCP-1) is suggested.ObjectiveTo measure the serum level of MCP-1 in ruptured CAs in different time intervals.MethodsWe measured the serum levels of MCP-1 in SAH patients who had CAs and compared it with that of MCP-1 in two control groups: including patients with SAH without CAs, and the normal population of blood donors. We also measured the MCP-1 levels in patients with CAs one week afterward to evaluate the effect of treatment. Serum level of MCP-1 was measured by a commercial ELISA assay.ResultsMean serum MCP-1 level in patients with SAH and CAs was 188.2168 Pg/ml and 331.3982 Pg/ml in the normal population. There was no statistically significant difference between serum levels of MCP-1 on the first (mean=188.2168 Pg/ml) and 7th days after SAH onset (mean=171.8450 Pg/ml) (p=0.739). Serum level of MCP-1 increased significantly as Glasgow Coma Scale decreased (p=0.078) and Hunt and Hess score increased (p=0.089).ConclusionOur results did not show an increasing MCP-1 serum level in patients with aneurysmal SAH. There was a relationship between poor clinical grade and MCP-1 levels in patients with CAs. MCP-1 may be a local inflammatory marker for cerebral aneurysms without systemic manifestation. Rahmanian A, et al. Iran J Immunol. 2015; 12(4):302-310.Keywords: Intracranial Aneurysm, Monocyte Chemoatractic Protein 1, Serum Level
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Page 311BackgroundLack of sufficient information on the mechanism of plasma exchange (PE) therapy in multiple sclerosis (MS), has limited this treatment to individual patients with severe relapses who have been refractory to other treatments. This is while PE is used very successfully as a first-line standard treatment in many other neuro-immune disorders. Recent data suggest that Treg/Th17 counterbalance may indicate the boundaries between promotion and regulation of inflammatory responses in MS and Treg/Th17 ratio may be useful as a marker for monitoring the efficiency of MS therapies.ObjectiveTo evaluate the effect of PE on the frequency and ratio of Treg/Th17 cells through concomitant measurement of the expression levels of Treg and Th17 lineage specific transcription factors, FOXP3 and RORC2, respectively.MethodsPeripheral blood mononuclear cells of 8 relapsed MS patients were obtained before and after a complete course of PE therapy and the FOXP3 and RORC2 mRNA levels were assayed using real-time PCR approach.ResultsNo significant change in the expression levels of individual transcription factors existed, but a significant increase in FOXP3/RORC2 ratio (p=0.036) was observed.ConclusionsOur results suggest that PE therapy influences Treg/Th17 ratio and this may be a mechanism by which this procedure exerts its improving effects in MS disease. Jamshidian A, et al. Iran J Immunol. 2015; 12(4):311-318.Keywords: Multiple Sclerosis, Plasma Exchange, Th17, Treg