Shiraz Institute for Cancer ResearchIranian Journal of Immunology1735-138314420171201CD4+ T Cells are Exhausted and Show Functional Defects in Chronic Lymphocytic Leukemia25726939322ENEsmaeilAllahmoradiDepartment of Immunology, School of Medicine, Mazandaran University of Medical Sciences,Sari, Iran2
Student Research Committee, Mazandaran University of
Medical Sciences, Sari, IranSaeidTaghilooDepartment of Immunology, School of Medicine, Mazandaran University of Medical Sciences,Sari, Iran2
Student Research Committee, Mazandaran University of
Medical Sciences, Sari, Iran0000-0002-8813-6046MohsenTehraniDepartment of Immunology, School of Medicine, Mazandaran University of Medical Sciences,Sari, Iran0000-0002-9292-4520HadiHossein-NattajDepartment of Immunology, School of Medicine, Mazandaran University of Medical Sciences,Sari, IranGhasemJanbabaeiGastrointestinal Cancer
Research Center, Mazandaran University of
Medical Sciences, Sari, IranRaminShekarrizGastrointestinal Cancer
Research Center, Mazandaran University of
Medical Sciences, Sari, IranHosseinAsgarian-OmranDepartment of Immunology, School of Medicine, Mazandaran University of Medical Sciences,Sari, IranImmunogenetics Research Center, School of Medicine, Mazandaran University of
Medical Sciences, Sari, Iran0000-0003-3816-8792Journal Article20171225<strong>Background:</strong> Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the western world. This health problem is caused due to the accumulation of mature B-lymphocytes in the peripheral blood and bone marrow. In the course of cancer, CD4+ T cells become “exhausted” and characterized with poor effector functions and the expression of multiple inhibitory receptors. <strong>Objective:</strong> To investigate the frequency and functional properties of exhausted CD4+ T lymphocytes in patients with CLL. <strong>Methods:</strong> Peripheral blood mononuclear cells were obtained from 25 untreated CLL patients and 15 healthy volunteers. CLL patients were clinically classified according to the Rai staging system. The frequency of CD4+/Tim-3+/PD-1+ cells was obtained by flow cytometry. To evaluate cell proliferation and cytokine production, CD4+ T cells were isolated and stimulated with phytohemagglutinin and PMA/ionomycin. Concentrations of IL-2, IFN-γ, TNF-α, and IL-10 were measured in the culture supernatants of stimulated cells by the ELISA technique. <strong>Results:</strong> The percentage of CD4+/Tim-3+/PD-1+ cells was significantly higher in CLL patients than that of healthy controls. CD4+ T cells from CLL patients showed lower proliferative responses, a lower production of IL-2, IFN-γ, and TNF-α, and a higher production of IL-10, compared to healthy controls. CD4+ T cells from CLL patients in advanced clinical stages showed more exhaustion features than those of early stages. <strong>Conclusion:</strong> Given that the exhaustion phase of T cells can be reversible, targeted blocking of immune inhibitory molecules could be a promising tool to restore the host immune responses against leukemic cells in CLL.https://iji.sums.ac.ir/article_39322_9029a913c61823fbc825e875436c2f97.pdfShiraz Institute for Cancer ResearchIranian Journal of Immunology1735-138314420171201CD40 Knocked Down Tolerogenic Dendritic Cells Decrease Diabetic Injury27028039323ENAzizMahmoudzadehDepartment of Bioscience and Biotechnology, Malek-Ashtar University of Technology, Tehran, IranAli AkbarPourfathollahDepartment of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, IranMohammad HosseinKarimiTransplant Research Center, Nemazee Hospital, Shiraz University of Medical Sciences, Shiraz, Iran0000-0002-2435-6277Seyed MohammadMoazzeniDepartment of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, IranJournal Article20171225<strong>Background:</strong> Type-1 diabetes (T1D) is an autoimmune disease in which T lymphocytes destroy insulin-producing β-cells. Control of self-reactive T lymphocytes and recovery of diabetic injury is the end point of T1D. <strong>Objective:</strong> To investigate generation of tolerogenic dendritic cells (tolDCs) as an innovative method of diabetes therapy. <strong>Methods:</strong> Lentivirus vector production was achieved by GIPZ mouse CD40 shRNA, psPAX2 and pMD2G plasmids DNA. Purified bone marrow derived DCs were treated with CD40 shRNA, and expression of CD40 and mRNA level were evaluated by flow cytometry and Real-Time PCR, respectively. CD40 knock-down DCs were injected into STZ-induced diabetic mice. Blood glucose; glucose tolerance test and weight were analyzed in different groups. <strong>Results:</strong> Mice treated with CD40 shRNA transfected DCs showed considerable differences in blood glucose, glucose tolerance, and weight compared to other groups. Also cytokine assays indicated an increase in IL-13 production in the CD40 shRNA group. <strong>Conclusion:</strong> In streptozotocin-induced diabetic mice model, administration of tolerogenic dendritic cells could improve diabetic parameters.https://iji.sums.ac.ir/article_39323_0df77a0d1ed3aa343ee20aa9a0900e73.pdfShiraz Institute for Cancer ResearchIranian Journal of Immunology1735-138314420171201Expression of Human Cytokine Genes Associated with Chronic Hepatitis B Disease Progression28129239324ENJournal Article20171225<strong>Background:</strong> Hepatitis viruses are non-cytopathic viruses that lead to the infection and pathogenesis of liver diseases as a result of immunologically mediated event. <strong>Objective:</strong> To investigate the expression of human inflammatory cytokines in chronic hepatitis B patients according to the severity of the infection. <strong>Methods:</strong> We recruited a total of 120 patients, 40 of whom from cirrhotic, 40 non-cirrhotic, and 40 acute flare chronic hepatitis B and 40 healthy controls. For all groups total cellular RNA was extracted from whole blood samples, genomic DNA was eliminated, and cDNA was synthesized using the RT2 first strand kit, as instructed by the manufacturer. The real-time profiler PCR array was performed on an a master cycler ep realplex and the data were analyzed using an online data analysis software. <strong>Results:</strong> Non-cirrhotic chronic hepatitis B patients were found to significantly upregulate interleukin 10 receptors that regulate the balance between T helpers 1 and 2. On the other hand, patients with cirrhosis were found to have significant upregulated interleukin 3 gene expression. <strong>Conclusion:</strong> Our finding suggests that upregulation of anti-inflammatory and downregulation of pro-inflammatory cytokines may play a roles in the progression of non-cirrhotic chronic hepatitis B patients to cirrhotic and acute flare. However, a multi-center study with a larger sample size is needed to confirm our findings.https://iji.sums.ac.ir/article_39324_2588cdefc3975f76193f48b014bb1140.pdfShiraz Institute for Cancer ResearchIranian Journal of Immunology1735-138314420171201Cytokine Profile of Leishmania Infantum Fucose-Mannose Ligand in Vaccinated Dogs in the Northwest of Iran29330539325ENBehnamMohammadi-Ghalehbin1Department of Parasitology and Mycology, School of Medicine, Shiraz University of Medical Sciences, Shiraz,Department of Microbiology, Immunology and Medical Parasitology, School of Medicine, Ardabil University of Medical Sciences, Ardabil, IranGholamrezaHatamBasic Sciences in Infectious Diseases Research Center, Shiraz University of Medical Sciences, Shiraz, IranBahadorSarkariBasic Sciences in Infectious Diseases Research Center, Shiraz University of Medical Sciences, Shiraz, IranMehdiMohebaliDepartment of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, IranZabihZareiDepartment of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, IranShahabBohlooliDepartment of Pharmacology and Toxicology, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, IranJournal Article20171225<strong>Background:</strong> Canine visceral leishmaniasis (CVL) caused by <em>Leishmania infantum</em> is endemic in the northwest and south of Iran. An appropriate vaccine can help to prevent and control visceral leishmaniasis in both humans and animals. Few studies have confirmed that the fucose-mannose ligand (FML) antigen of <em>Leishmania donovani</em> produced protective immunity in dogs against CVL. <strong>Objective:</strong> To evaluate the immune responses of vaccinated dogs against FML antigen of <em>L. infantum</em>. <strong>Methods:</strong> We isolated the FML antigen from native <em>L. infantum</em> and vaccinated the dogs with FML-saponin in an endemic area of VL in Iran to evaluate the immune responses of vaccinated dogs against this antigen. <strong>Results:</strong> Our results indicated a significant increase in the expression of IFN-γ, IL-10 and IL-13, but not IL-12A, gene transcripts in PBMCs of FML-saponin vaccinated dogs in comparison with controls. Our findings showed a significant difference in the ratio of IFN-γ/IL-10 mRNA expression in FML-saponin vaccinated dogs in comparison with two control groups. Moreover, a significant level of anti-FML antibodies was detected in serum of vaccinated dogs. <strong>Conclusion:</strong> These findings showed that FML-saponin stimulates both Th1 and Th2 immune responses with predominant Th1 and strong humoral immune responses to produce protective immunity against CVL.https://iji.sums.ac.ir/article_39325_45d3eb2ac3f26d151dfbbd45d06f623e.pdfShiraz Institute for Cancer ResearchIranian Journal of Immunology1735-138314420171201The Reaction of Placental GRP78 Protein with Sera from Women with Multiple Sclerosis30631539326ENBehrouzGharesi-FardDepartment of Immunology, School of MedicineInfertility Research Center, Shiraz University of Medical Sciences, Shiraz, Iran0000-0002-0162-3395MaryamZareDepartment of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, IranEskandarKamali-SarvestaniDepartment of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, IranAutoimmune Diseases Research Center, Shiraz University of Medical Sciences, Shiraz, IranJournal Article20171225<strong> </strong><br /> <strong>Background:</strong> Multiple Sclerosis (MS) with four different types is one of the well studied autoimmune diseases of the central nervous system. Generally, two-thirds of MS patients are females who are at risk of pregnancy-related complications. Inappropriate responses of mother’s immune system, such as antibody production against placental proteins, may lead to pregnancy-related disorders. The association between pregnancy complications and some autoantibodies including anti-phospholipid and anti-angiotensin II type-1 receptor antibodies are clear examples in this regard. <strong>Objective:</strong> To investigate the probable placental antigens that might be targeted by the antibodies in the sera of MS patients. <strong>Methods:</strong> Total placental proteins were extracted from normal fresh placentas and were separated using two-dimensional gel electrophoresis (2-DE) technique. The separated proteins were transferred onto a Polyvinylidene Fluoride (PVDF) membrane and blotted with the pooled sera of MS women or healthy controls (20 individuals in each group). The differentially blotted spot was identified by mass spectrometry and confirmed by western blot technique. <strong>Results:</strong> The results indicated that the women afflicted with MS had an antibody against placental HSP70kDa protein 5 (GRP78). <strong>Conclusion:</strong> In the present study, a new placental autoantigen candidate, which was targeted by antibody present in MS women sera, was found. The clinical importance of this finding regarding pregnancy complications in MS patients should be investigated by further experiments.https://iji.sums.ac.ir/article_39326_476a776d5c4697bf05614db9f53b2251.pdfShiraz Institute for Cancer ResearchIranian Journal of Immunology1735-138314420171201Evaluation of the miRNA-146a and miRNA-155 Expression Levels in Patients with Oral Lichen Planus31632439327ENFatemehAhmadi-MotamayelDental Research Center, Department of Oral Medicine, Hamadan University of Medical Sciences, Hamadan, IranZeynabBayatDental Research Center, Department of Oral Medicine, Hamadan University of Medical Sciences, Hamadan, IranMehrdadHajilooiDepartment of Immunology, Medical School, Hamadan University of Medical Sciences, Hamadan, IranSorooshShahryar-HesamiDepartment of Immunology, Medical School, Hamadan University of Medical Sciences, Hamadan, IranAliMahdavinezhadDepartment of Genetic and Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, IranLidaSamieDental Research Center, Department of Oral Medicine, Hamadan University of Medical Sciences, Hamadan, IranGhasemSolgiDepartment of Immunology, Medical School, Hamadan University of Medical Sciences, Hamadan, IranJournal Article20171225<strong>Background: </strong>Oral Lichen Planus (OLP) is a chronic autoimmune disease that could be considered as a potential premalignant status.<strong> Objective:</strong> To evaluate the miRNA-146a and miRNA-155 expression levels in patients with oral Lichen planus lesions compared to healthy subjects with normal oral mucosa. <strong>Methods:</strong> Forty patients with oral lichen planus and 18 healthy age and gender-matched controls were recruited in this case-control study. Oral lichen planus was diagnosed clinically and pathologically. The expression levels of two miRNAs in peripheral blood samples were determined using commercial TaqMan MicroRNA Assays. Relative quantification of gene expression was calculated by the 2<sup>-ΔΔct</sup> method. <strong>Results:</strong> The expression levels of miRNA-146a and miRNA-155 in patients with oral Lichen planus were significantly higher than the of the healthy control group. Also, a direct but insignificant correlation was found between miRNA-155 and miRNA-146a expression levels among the patient group. <strong>Conclusion:</strong> Our findings indicate that miRNA-146a and miRNA-155 could be potential biomarkers for the immunopathogenesis of oral lichen planus.https://iji.sums.ac.ir/article_39327_e729b574aa4188e9b4d1743a01ba5feb.pdfShiraz Institute for Cancer ResearchIranian Journal of Immunology1735-138314420171201Non-Viable Lactobacillus Casei Beneficially Modulates Poly I:C Immune Response in Co-Cultures of Human Cells32533939328ENElisaVintiñiLARIVENOA, Faculty of Agronomy and Zootechnics, National University of Tucumán, Florentino Ameghino S/N, Tucumán, ArgentinaMarcelaMedinaInstitute of Microbiology, Faculty of Biochemistry, Chemistry and Pharmacy, National University of Tucumán, CCT-CONICET (National Council of Scientific and Technical Research), Ayacucho 471, CP 4000, San Miguel de Tucumán, Tucumán, ArgentinaJournal Article20171225<strong> </strong><br /> <strong>Background:</strong> Polyinosinic:polycytidylic acid (Poly-IC) has been used as a viral stimulus to mimic <em>in vivo</em> and <em>in vitro</em> infection induced by some viruses. <strong>Objective:</strong> To determine whether non-viable <em>Lactobacillus casei</em> CRL431 (LcM) can modulate the immune response induced by Poly I:C in co-culture models of peripheral blood mononuclear cells (PBMC) and A549 cells. <strong>Methods:</strong> T and NK cell activation was evaluated by flow cytometry and levels of TNF-α, IFN-γ, IL-10, IL-29, and IL-17 by ELISA. Cells in direct contact with A549 (PBMC-A549) and cells with no contact with it (PBMC//A549) were used for this purpose. PBMCs alone and both co-culture systems were stimulated for 24 h with the following stimuli: LPS (10 µg/ml), LcM (10<sup>6</sup> UFC/ml), Poly I:C (2 µg/ml), Poly I:C+LcM, and LcM (3 h)+Poly I:C. Moreover, unstimulated cells were used as a control. <strong>Results:</strong> Poly I:C and LcM (3 h)+Poly I:C in PBMC-A549 showed a significant increase in the percentage of CD8+ expression (p<0.05). All stimuli induced significant activation from T CD4+, CD8+ cells compared with unstimulated PBMCs in both co-culture cells system. However, activation percentages were higher in direct co-culture. Poly I:C induced a higher level of pro-inflammatory TNF-α and IFN-γ cytokines as well as IL-17 and IL-29 with lower IL-10 levels in both co-culture systems while LcM induced a beneficial pattern of cytokines that would regulate Poly I:C effect. <strong>Conclusion:</strong> This <em>in vitro</em> model allowed us to highlight the potential of LcM as a modulator of anti-viral immune response and suggest its potential use in formulations against RNA respiratory viruses.https://iji.sums.ac.ir/article_39328_f12863523edece69a6bfabf6e8c2692e.pdfShiraz Institute for Cancer ResearchIranian Journal of Immunology1735-138314420171201IL-6/IL-10 Ratio as A Prognostic and Predictive Marker of the Severity of Inherited Epidermolysis Bullosa34034939329ENMarilinaTampoiaClinical Pathology Laboratory, Polyclinic of Bari, Department of Biomedical Sciences and Human Oncology, University of Bari, Piazza Giulio Cesare 11, 70124 Bari, ItalyLetiziaAbbracciaventoClinical Pathology Laboratory, Polyclinic of Bari, Department of Biomedical Sciences and Human Oncology, University of Bari, Piazza Giulio Cesare 11, 70124 Bari, ItalyMarellaMorroneClinical Pathology Laboratory, Polyclinic of Bari, Department of Biomedical Sciences and Human Oncology, University of Bari, Piazza Giulio Cesare 11, 70124 Bari, ItalyRuggieroFumaruloClinical Pathology Laboratory, Polyclinic of Bari, Department of Biomedical Sciences and Human Oncology, University of Bari, Piazza Giulio Cesare 11, 70124 Bari, ItalyJournal Article20171225<strong>Background:</strong> Recent studies have shown that cytokines have an important role in the pathogenesis of inflammatory diseases and can be used as prognostic markers. <strong>Objective:</strong> To evaluate the IL-6/IL-10 ratio in patients with Inherited Epidermolysis Bullosa (EB) as a prognostic marker. <strong>Methods:</strong> Serum levels of IL-6 and IL-10 were measured in 13 patients with recessive dystrophic EB (RDEB) as well as 10 with EB Simplex (EBS), and in 18 healthy subjects. Receiver Operating Characteristics (ROC) analyses were used to assess the diagnostic accuracy of the IL-6/IL-10 ratio for detecting severe form of EB. <strong>Results:</strong> The IL-6/IL-10 ratio was statistically higher in RDEB patients than in EBS patients and healthy subjects. The IL-6/IL-10 ratio significantly correlated with BEBS score. <strong>Conclusion:</strong> Our findings suggest that IL-6/IL-10 ratio >5.6 has a good diagnostic accuracy to identify patients with the highest severity of disease.https://iji.sums.ac.ir/article_39329_968e055c5ad01db96b722bbec2e44ab9.pdf