@article { author = {Faghih, Zahra and Sadat Shobeiri, Saeideh and Ariafar, Ali and Sarkarian, Mohsen and Zeighami, Shahryar and Nazari, Nazanin and Abbasi-Sarvak, Saeed and Erfani, Nasrollah}, title = {CD8+ T Lymphocyte Subsets in Bladder Tumor Draining Lymph Nodes}, journal = {Iranian Journal of Immunology}, volume = {13}, number = {4}, pages = {237-248}, year = {2016}, publisher = {Shiraz Institute for Cancer Research}, issn = {1735-1383}, eissn = {1735-367X}, doi = {}, abstract = {Background: Cytotoxic CD8+ T cells, as essential parts of the adaptive immune system, play pivotal roles in anti-tumor immune responses. It is well documented that cytokine expression profiles and activation status of these cells during anti-tumor immune responses affect the outcome of host-tumor interaction. Objective: To investigate the percentages of CD8+ lymphocytes and their subsets in tumor draining lymph nodes of patients with bladder cancer. Methods: Forty-five patients with bladder cancer, candidate for radical cystectomy, were recruited. Mononuclear cells were isolated from draining lymph nodes using Ficoll-Hypaque gradient centrifugation, and were activated by PMA/Ionomycin in the presence of Golgi inhibitors. The cells were then permeabilized and stained with appropriate flourochrome conjugated antibodies against CD3, CD8, IFN-γ, IL-17 and IL-4 molecules. Data were collected on a fourcolor flow cytometer and analyzed by CellQuestPro software. Results: Despite no difference in the frequency of IL-17 producing CD8+ (Tc17) lymphocytes, the mean expression of IL-17 in this subset was significantly elevated in high-grade patients (p=0.011). The percentage of double positive IFN-γ/IL-17 CD8+ lymphocytes was also significantly increased in node positive patients compared to node negative ones (p=0.046). Our results also demonstrated that the percentage of IFN-γ producing CD8+ (Tc1) lymphocytes was significantly increased in the patients with higher histological grade compared to those with lower ones (p=0.038). Conclusion: IFN-γ and IL-17 producing CD8+ T cells may increase in advanced stages of bladder cancer, but their correlation with tumor prognosis remains to be investigated.}, keywords = {Bladder Cancer,Lymph Node,CD8+ lymphocytes,Tc1,Tc2,Tc17}, url = {https://iji.sums.ac.ir/article_39276.html}, eprint = {https://iji.sums.ac.ir/article_39276_b4a0d75e62ba8bf71d6ed4a8d8473928.pdf} } @article { author = {Yazdani, Mohammadreza and Khosropanah, Shahdad and Hosseini, Ahmad and Doroudchi, Mehrnoosh}, title = {Resting and Activated Natural Tregs Decrease in the Peripheral Blood of Patients with Atherosclerosis}, journal = {Iranian Journal of Immunology}, volume = {13}, number = {4}, pages = {249-262}, year = {2016}, publisher = {Shiraz Institute for Cancer Research}, issn = {1735-1383}, eissn = {1735-367X}, doi = {}, abstract = {Background: Atherosclerosis is a chronic inflammatory disease affecting large and medium arteries. CD4+ T cells are known to play a role in the progression of the disease. CD4+CD25+Foxp3+ natural Treg (nTreg) cells seem to have a protective role in the disease and their reduction in acute coronary syndrome is recently shown. Objective: To investigate the frequency of nTreg subsets in the peripheral blood of patients with atherosclerosis. Methods: Confirmation of atherosclerosis was done by angiography and 15 ml heparinized blood was obtained from each of the 13 nondiabetic patients and 13 non-diabetic, non-smoker individuals with normal/insignificant coronary artery disease which was also confirmed by angiography. Lipid profiles of the patients and controls were measured at the time of sampling. Mononuclear cells were used for both RNA extraction and immunophenotyping by real-time PCR and flowcytometry techniques, respectively. Results: In natural Treg subsets, the frequency of CD4+CD45RO-CD25+Foxp3lo T-cells (resting nTregs) was greater in controls than patients (p=0.02). The frequency of CD4+CD45RO+CD25hiFoxp3hi T-cells (activated nTregs) was significantly higher in controls compared with patients (p=0.02). However, the frequency of CD4+CD25+CD45RO+Foxp3- T-cells (effector/memory) increased in patients compared with controls (p=0.01). Both the MFI and gene expression of Foxp3 were higher in control group than in patients (p=0.015 and p=0.017, respectively). Moreover, the TGF-β gene expression showed a decrease in the peripheral blood mononuclear cells of patients compared with controls (p=0.03). Conclusion: Decrease in both subsets of resting and activated nTregs along with a decrease in the expression of Foxp3 and TGF-β genes in patients with atherosclerosis suggests phenotypic changes in these subsets, which may as well be correlated with a more inflammatory profile in their lymphocytes.}, keywords = {Atherosclerosis,Natural Tregs,CD45RO,FOXP3}, url = {https://iji.sums.ac.ir/article_39277.html}, eprint = {https://iji.sums.ac.ir/article_39277_6b0ea33e02b7546a92e2518f0b37b878.pdf} } @article { author = {Feyzi, Reza and Boskabady, Mohammad Hossein and Seyed hosseini Tamijani, Seyedeh Masoumeh and Rafatpanah, Houshang and Rezaei, Seyed Abdolrahim}, title = {The Effect of Safranal on Th1/Th2 Cytokine Balance}, journal = {Iranian Journal of Immunology}, volume = {13}, number = {4}, pages = {263-273}, year = {2016}, publisher = {Shiraz Institute for Cancer Research}, issn = {1735-1383}, eissn = {1735-367X}, doi = {}, abstract = {Background: Several biological and medical benefits of Saffron, Crocus sativus (Iridaceae), have been demonstrated. However, mechanisms of actions for purified constituents are greatly unknown. Objective: To examine the effects of Safranal, a main constituent of Saffron stigma, on cell viability and cytokine profile of peripheral blood mononuclear cells (PBMC) were examined. Methods: Effects of Safranal at 0.1, 0.5 and 1 mM concentrations were evaluated on cell viability and production of interleukin 4 (IL-4), IL-10 and interferon-γ (IFN-γ) from non-stimulated and phytohemagglutinin (PHA) stimulated PBMCs, compared to 0.1 mM dexamethasone and saline. Results: In stimulated cells, different concentrations of Safranal caused significant decrease of lymphocytes viability (p<0.001 for all concentrations). All concentrations of Safranal inhibited IFN-γ and IL-10 secretion in stimulated cells (p<0.01). In addition, high concentration of Safranal significantly decreased cell viability of non-stimulated PBMCs (p<0.001). The effect of 1 mM Safranal on IL-4 secretion was less than dexamethasone (p<0.05). Safranal showed a stimulatory effect on IFN-γ secretion in non-stimulated cells. The IFN-γ/IL-4 ratio at the presence of two higher Safranal concentrations both in non-stimulated and stimulated cells were significantly higher than those of control and PHA stimulated groups, respectively (p<0.05). Conclusion: The IFN-γ/IL-4 ratio increases in the presence of Safranal which indicates an effect on Th1/Th2 balance. Therefore, Safranal may have therapeutic effects in inflammatory diseases associated with Th1/Th2 imbalance.}, keywords = {Cell Viability,Cytokine,Safranal,Th1,Th2}, url = {https://iji.sums.ac.ir/article_39278.html}, eprint = {https://iji.sums.ac.ir/article_39278_b582d4d6c450a7c199f60cf2d24f535f.pdf} } @article { author = {Moravej, Ali and Karimi, Mohammad-Hossein and Geramizadeh, Bita and Hossein Aghdaie, Mahdokht and Kohi-Hoseinabadi, Omid and Ebrahimnezhad, Salimeh}, title = {Effect of Mesenchymal Stem Cells on ILT3 Expression in the Splenocytes of Skin Graft Recipient Mice}, journal = {Iranian Journal of Immunology}, volume = {13}, number = {4}, pages = {274-288}, year = {2016}, publisher = {Shiraz Institute for Cancer Research}, issn = {1735-1383}, eissn = {1735-367X}, doi = {}, abstract = {Background: Mesenchymal stem cells (MSCs) are considered as effective therapeutic cells in transplantation due to their immunomodulatory activities. However, precise mechanism of MSCs immunomodulatory activity is not completely understood. Objectives: To study the role of Immunoglobulin-like transcripts-3 (ILT3) immunomodulatory receptor in immune tolerance induced by MSCs in skin transplantation model and induction of tolerogenic dendritic cells (Tol-DCs) by MSCs through up-regulation of ILT3. Methods: C57BL/6 skin grafts were transplanted to the back of BALB/c mice. Recipient mice received MSCs on days 0, 1 and 2 post transplantation. On days 2, 5 and 10 post skin transplantation, ILT3 and forkhead box P3 (FOXP3) expression in the spleens of MSCs treated mice were evaluated. Furthermore, MSCs and DCs were co-cultured in cell culture plates and transwell systems. Then, the expressions of ILT3 mRNA and protein in MSC-treated DCs were evaluated. Additionally, MSC-treated DCs were co-cultured with allogeneic T-cells and FOXP3 expression in T-cells was evaluated. Results: The expression of ILT3 and FOXP3 were higher in the splenocytes of MSCs-treated mice early post-transplantation. Furthermore, we observed that MSC-treated DCs can increase FOXP3 expression in Tcells. But, we could not find any differences in ILT3 expression between MSC-treated DCs and untreated ones. Conclusion: One of the mechanisms underlying MSCs immunomodulatory function could be up-regulating ILT3 expression in splenocytes. But our results did not support the hypothesis that MSCs induce Tolergenic DCs by upregulation of ILT3.}, keywords = {ILT3, Immunomodulation,MSCs, Transplantation}, url = {https://iji.sums.ac.ir/article_39279.html}, eprint = {https://iji.sums.ac.ir/article_39279_2b4d8b4d3e783cae3e69643587222d2e.pdf} } @article { author = {Meshkat, Zahra and Teimourpour, Amir and Rashidian, Samira and Arzanlou, Mohsen and Teimourpour, Roghayeh}, title = {Immunogenicity of a DNA Vaccine Encoding Ag85a-Tb10.4 Antigens from Mycobacterium Tuberculosis}, journal = {Iranian Journal of Immunology}, volume = {13}, number = {4}, pages = {289-295}, year = {2016}, publisher = {Shiraz Institute for Cancer Research}, issn = {1735-1383}, eissn = {1735-367X}, doi = {}, abstract = {Background: Tuberculosis is a life threatening disease that is partially prevented by BCG vaccine. Development of more effective vaccines is an urgent priority in TB control. Ag85a and Tb10.4 are the members of culture filter protein (CFP) of M. tuberculosis that have high immunogenicity. Objective: To analyze the immunogenicity of Ag85a-Tb10.4 DNA vaccine by enzyme-linked immunosorbent assay (ELISA). Methods: In this study a previously described plasmid DNA vaccine encoding Ag85a-Tb10.4 was used to examine its capability in the stimulation of immune responses in an animal model. Female BALB/c mice were vaccinated with 100 μg of purified recombinant vector intramuscularly 3 times at two-week intervals and the levels of five cytokines including IFN-γ, IL-12, IL-4, IL-10 and TGF-β were measured. Results: The levels of IFN-γ and IL-12 for the mice following immunization with Ag85A-Tb10.4 was significantly greater than that of the BCG and control group (p<0.05). However there was no significant difference in the levels of IL-4, IL-10 and TGF-β between groups. Conclusion: IFN-γ and IL-12 Th1 cytokines increased significantly in mice vaccinated with Ag85a-TB10.4 DNA vaccine in comparison to the control and BCG groups. Our results may serve as groundwork for further research into the prevention and treatment of tuberculosis.}, keywords = {Antigen 85,BALB/c Mice,DNA vaccine,Mycolyltransferase,Tb10.4}, url = {https://iji.sums.ac.ir/article_39280.html}, eprint = {https://iji.sums.ac.ir/article_39280_c8d102fc79c1495a49c99b3c64c2ca2a.pdf} } @article { author = {Gharesi-Fard, Behrouz and Mobasher-Nejad, Fatemeh and Nasri, Fatemeh}, title = {The Expression of T-Helper Associated Transcription Factors and Cytokine Genes in Pre-Eclampsia}, journal = {Iranian Journal of Immunology}, volume = {13}, number = {4}, pages = {296-308}, year = {2016}, publisher = {Shiraz Institute for Cancer Research}, issn = {1735-1383}, eissn = {1735-367X}, doi = {}, abstract = {Background: Pre-eclampsia (PE) is known as a main factor contributing to fetomaternal mortality, which might affect 2-8% of all pregnancies after the twentieth week of gestation. The balance of T helper subsets is essential to sustain a normal pregnancy and preventing fetomaternal complications. Objective: To investigate differences in the levels of transcription factors and cytokine gene expression of Th1/Th2/Th17/Treg subsets within decidual and chorionic layers of placentas from 15 PE-afflicted and 15 healthy Iranian women in their third trimester of pregnancy. Methods: Using Quantitative real-time PCR (Q-PCR), The expression of T-BET, GATA-3, ROR-ɣt, FOXP3, and cytokines, including IL-1, IL-6, TNF-α, IFN-γ, IL-4, IL-31, IL-17, IL-23, TGF-β1, TGF-β2, TGF-β3, and IL-35 in the placenta were compared at mRNA levels between groups. Results: FOXP3 and GATA-3 were significantly down-regulated, while T-BET was up-regulated in PE deciduae compared to the control group (p<0.0001, p<0.02, and p<0.01, respectively). Concerning the chorionic samples, FOXP3 significantly decreased, while ROR-γt increased in the PE placentas compared to the healthy ones (p<0.0006 and p<0.02, respectively). Besides, most inflammatory cytokines were up-regulated, while anti-inflammatory cytokines were down-regulated in the PE placentas. Additionally, TNF-α/IL-35, IFN-ɣ/IL-35, IL- 6/IL-35, and IL-23/IL-35 ratios were significantly higher (p<0.01) and IL-35/IL-17 ratio was significantly lower (p<0.05) in the pre-eclamptic patients compared to the healthy controls. Conclusion: Our results shed more light on the contribution of Th1/Th2/Th17/Treg balance within placenta in the fate of a normal pregnancy. Moreover, regulatory T cells and IL-35 seem to play a central role in the regulation of all subsets.}, keywords = {Cytokines expression,IL-35,Pre-eclampsia,Transcription factor}, url = {https://iji.sums.ac.ir/article_39281.html}, eprint = {https://iji.sums.ac.ir/article_39281_5c34513cd2e4333b3fd81cf659b5a4a6.pdf} } @article { author = {Tavakkol Afshari, Zeinab and Rahimi, Hamid Reza and Ehteshamfar, Seyed Morteza and Ganjali, Rashin and Tara, Fatemeh and Shapouri Moghadam, Abbas}, title = {Tumor Necrosis Factor-α and Interleukin-1- β Polymorphisms in Pre-Eclampsia}, journal = {Iranian Journal of Immunology}, volume = {13}, number = {4}, pages = {309-316}, year = {2016}, publisher = {Shiraz Institute for Cancer Research}, issn = {1735-1383}, eissn = {1735-367X}, doi = {}, abstract = {Background: Pre-eclampsia is the most common critical condition during pregnancy. Plasma concentrations of tumor necrosis factor-alpha (TNF-α) and interleukin-1-beta (IL-1β) increase in pregnant women with pre-eclampsia, compared to normal pregnant women. Objective: To investigate the polymorphisms of IL-1β (C+3954T), TNF-α (G- 308A), and (G-238A) in preeclemptic women northeastern Iran. Methods: This study was conducted on 153 preeclamptic women (case group) and 150 healthy pregnant women (control group), admitted to Ghaem and Imam Reza hospitals of Mashhad, Iran. IL-1β (C+3954T), TNF- α (G-238A) and TNF-α (G-308A) gene polymorphisms in the promoter region were screened by polymerase chain reaction. Data were analyzed, using SPSS version 16.0. Results: The mean age of the participants in the case and control groups was 28.2 ± 6.1 and 27.1 ± 6.3 years, respectively (P=0.68). The frequency of G-308A polymorphism was significantly higher in the case group, compared to the control group (p<0.001). However, no significant relationship was found between IL-1β genotype and pre-eclampsia (p=0.39). The frequency of TNF- α (G-238A) AA genotype was significantly higher in the case group, while GG genotype was less frequently detected in the case group, compared to the control group (p<0.001 for both genotypes). Moreover, the frequencies of AA genotypes of -238 TNF-α and G- 308A polymorphisms were significantly higher in the case group, compared to the control group (p<0.001). Conclusion: The significant correlation between inflammation promoting genotypes of TNF-α and Pre-eclampsia is noteworthy and provides evidence on the contribution of immune related genes in this disease.}, keywords = {Gene Polymorphism,Interleukin-1β,PCR-RFLP,Pre-eclampsia,Tumor necrosis Factor-α}, url = {https://iji.sums.ac.ir/article_39282.html}, eprint = {https://iji.sums.ac.ir/article_39282_dd5a9a756f751b19663f211ac11d7f47.pdf} } @article { author = {Sobhan, Mohammad Reza and Farshchian, Mahmood and Hoseinzadeh, Ali and Ghasemibasir, Hamid Reza and Solgi, Ghasem}, title = {Serum Levels of IL-10 and IL-22 Cytokines in Patients with Psoriasis}, journal = {Iranian Journal of Immunology}, volume = {13}, number = {4}, pages = {317-323}, year = {2016}, publisher = {Shiraz Institute for Cancer Research}, issn = {1735-1383}, eissn = {1735-367X}, doi = {}, abstract = {Background: As a chronic inflammatory condition, psoriasis results from an interaction between genetic and immunologic factors in a predisposing environment. In spite of compelling evidence for the role of T cells and cytokines in psoriasis, interleukin (IL)- 10 and IL-22 have not been sufficiently investigated. Objective: To assess the serum levels of IL-10 and IL-22 in patients with psoriasis compared to healthy controls. Methods: A total of 28 patients with psoriasis were compared with 28 age and sexmatched healthy subjects. Psoriasis Area and Severity Index (PASI) criteria were used to measure the severity of the disease. Serum levels of IL-10 and IL-22 were measured in both groups and compared. Results: The mean serum level of IL-10 was 89.5±18.7 in patients compared to 117.2±23.4 pg/ml in the controls (p=0.36). Also, serum level of IL-22 was 284.1±49.7 in patients versus 425.4±82.8 pg/ml in control group (p=0.17). There was a significant direct correlation between levels of IL-10 and IL-22 in patients group (p=0.0005). The clinical severity of psoriasis was significantly correlated with high levels of IL-22 (p<0.0001).Conclusions: The decreased levels of IL-10 in psoriatic patients and direct correlation between higher levels of IL-22 and disease severity support the clinical implication of both cytokines in psoriasis.}, keywords = {IL-10,IL-22,Psoriasis}, url = {https://iji.sums.ac.ir/article_39283.html}, eprint = {https://iji.sums.ac.ir/article_39283_e5b18182232933846781ba6fa538274d.pdf} }