Bahador Bagheri; Bahram Sohrabi; Aliakbar Movassaghpur; Siminozar Mashayekhi; Afagh Garjani; Mehriar Shokri; Mohammad Noori; Alireza Garjani
Volume 9, Issue 3 , September 2012, , Pages 149-158
Abstract
Background: Toll like receptors (TLRs) are well recognized players in inflammatory conditions. Among them TLR-4 is involved in chronic inflammatory processes such as formation of atherosclerotic plaques. Objective: The present study was aimed to examine the effects of percutanoeus coronary intervention ...
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Background: Toll like receptors (TLRs) are well recognized players in inflammatory conditions. Among them TLR-4 is involved in chronic inflammatory processes such as formation of atherosclerotic plaques. Objective: The present study was aimed to examine the effects of percutanoeus coronary intervention (PCI) as a revascularization method on monocyte expression of hTLR-4 and on the serum levels of two proinflammatory cytokines (TNF-α and IL-1β). Methods: Blood samples were obtained from 41 patients with stable angina who were candidates for PCI. The samples were collected immediately before and 2h and 4h after PCI. The expression of hTLR-4 on CD14+ monocytes and the serum levels of TNF-α and IL-1β were measured using flowcytometry and ELISA techniques, respectively. Results: By comparing the frequency of circulating hTLR-4+/CD14+ monocytes at different time points, it was observed that PCI procedure up regulates the monocyte expression of hTLR-4 (p<0.05). The increase in expression was associated with the elevation of the serum levels of proinflammatory cytokines (p<0.05). There was a significant correlation between monocyte expression of hTLR-4 and serum levels of TNF-α and IL-1β only before PCI. In spite of parallel increase in the serum levels of proinflammatory cytokines and the monocyte expression of hTLR-4, the correlation did not attain a significant level after PCI intervals. Conclusion: PCI is positively associated with an increase in the monocyte expression of hTLR-4. It is also associated with the elevation in the serum levels of proinflmmatory cytokines. These findings suggest that hTLR-4 monocyte expression may be used as a potential prognostic tool in patients with stable angina undergoing PCI.
Nader Tajik; Tohid Kazemi; Aliakbar Delbandi; Ahad Ghods; Alireza Salek Moghaddam
Volume 3, Issue 4 , December 2006, , Pages 150-156
Abstract
Background: In addition to Human Leukocyte Antigens (HLA) compatibility, gene polymorphisms in cytokines might also be important in the quality of allogeneic immune response. Objective: To evaluate the influence of HLA-DR matching and a number of cytokine gene polymorphisms on acute rejection after living-unrelated ...
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Background: In addition to Human Leukocyte Antigens (HLA) compatibility, gene polymorphisms in cytokines might also be important in the quality of allogeneic immune response. Objective: To evaluate the influence of HLA-DR matching and a number of cytokine gene polymorphisms on acute rejection after living-unrelated donor (LURD) kidney transplantation. Methods: A total of 42 renal transplants performed at Hashemi Nejad Kidney Hospital (Tehran/Iran) and followed up for 3 months post-transplantation were included. Using PCR-SSP, HLA-DR alleles (DR1- 18) of recipients and donors and gene polymorphisms in TNF-a, TGF-b1, IL-10, IL- 6, and IFN-g of recipients were determined. Results: Acute rejection was observed in 11(26.2%) of renal recipients. The frequency of one and two HLA-DR mismatches in rejector group was 2(18.2%) and 9(81.8%) and in non-rejector group was 13(41.9%) and 17(54.8%), respectively. HLA-DR incompatibility was not significantly higher in rejector (1.82 0.40) compared with non-rejector (1.52 0.57) recipients (P=0.069) and more than half of non-rejectors had completely mismatched HLA-DR antigens with donors. Polymorphisms associated with the mentioned cytokines had no correlation with acute rejection. Conclusion: The predictive value of HLA-DR mismatching for acute rejection is not as prominent in LURD kidney transplantation as in the cadaveric one. In addition, we failed to demonstrate an association between combined cytokine genotypes and HLA-DR matching with acute rejection. Further and more detailed immunogenetic investigations are required in order to have a better prediction of the transplant outcome.
Mohamed Shehata Ali Mohamed
Volume 12, Issue 3 , September 2015, , Pages 156-165
Abstract
The introduction of ex vivo lung perfusion (EVLP) in the practice of lung transplantation has allowed the reconditioning of the marginal grafts and their conversion into transplantable grafts. In addition, EVLP can provide a platform for the application of various preventive measures to decrease the ...
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The introduction of ex vivo lung perfusion (EVLP) in the practice of lung transplantation has allowed the reconditioning of the marginal grafts and their conversion into transplantable grafts. In addition, EVLP can provide a platform for the application of various preventive measures to decrease the incidence of post-transplant complications. While the Toronto team targets the attenuation of the cytokine production within the graft through gene therapy to up-regulate IL-10, other measures could be applied to achieve significant attenuation of the cytokine load of the graft. This manuscript provides a short overview on the importance of the attenuation of the cytokine production within the transplanted lung grafts and some possible strategies to achieve this goal.
Mehdi Mahdavi; Masoumeh Ebtekar; Fereidoun Mahboudi; Hamidreza Korram Khorshid; Fatemeh Rahbarizadeh; Kayhan Azadmanesh; Haydeh Darabi; Farzaneh Pourasgari; Zuhair Mohammad Hassan
Volume 6, Issue 4 , December 2009, , Pages 163-173
Abstract
Background: Cell mediated immunity, especially cytotoxic T cell responses against HIV-1 infection, plays a critical role in controlling viral replication and disease progres-sion. DNA vaccine is a novel technology which is known to stimulate strong cellular immune responses. Many DNA vaccines have been ...
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Background: Cell mediated immunity, especially cytotoxic T cell responses against HIV-1 infection, plays a critical role in controlling viral replication and disease progres-sion. DNA vaccine is a novel technology which is known to stimulate strong cellular immune responses. Many DNA vaccines have been tested for HIV infection but there is still no effective vaccine against this infection. Construction of a vaccine consisting of multiple conserved and immunogenic epitopes may increase vaccine efficacy. Objective: In the present study, a DNA vaccine candidate constructed from HIV-1 P24-Nef was evaluated and cellular immune responses were assessed in murine BALB/c model. Methods: HIV-1 P24-Nef gene was cloned in pCDNA3.1 expression vector. Mice were immunized with DNA construct and IL-4 and IFN-γ evaluation was per-formed using ELISPOT. Cytotoxicity response was evaluated with Granzyme B ELIS-POT assay and lymphocyte proliferation was evaluated with LTT assay. Results: Analysis of immune responses showed that, compared to control groups, the candidate vaccine induced production of higher levels of both IL-4 and IFN-γ (p<0.05). Cytotox-icity and lymphocyte proliferation responses of mice vaccinated with the candidate vac-cine were significantly increased compared to control groups (p<0.05). Conclusion: HIV-1 P24-Nef DNA construct displayed strong immunogenicity in a murine model.
Xiaoying Wang; Keye Xu; Sisi Chen; Yan Li; Mingcai Li
Abstract
Interleukin-1 family 7 (IL-1F7) is a novel member of IL-1F cytokines. IL-1F7 is more commonly known as IL-37. IL-37 join the α-subunit of the IL-18 receptor, or IL-18 binding protein (IL-18BP), and binding of these proteins can enhance the IL-18 suppression. IL-37 also translocates to the cell ...
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Interleukin-1 family 7 (IL-1F7) is a novel member of IL-1F cytokines. IL-1F7 is more commonly known as IL-37. IL-37 join the α-subunit of the IL-18 receptor, or IL-18 binding protein (IL-18BP), and binding of these proteins can enhance the IL-18 suppression. IL-37 also translocates to the cell nucleus and affects gene transcription. IL-37 inhibits the phosphorylation of p38 mitogen-activated protein kinases. Almost all reports showed that IL-37 has remarkable anti-inflammatory activity. IL-37 plays an important role in a variety of inflammatory and autoimmune diseases, as well. Recently, studies demonstrated that the expression of IL-37 is abnormal in many diseases such as inflammatory bowel diseases, inflammatory respiratory diseases, atherosclerosis, hepatitis, obesity, contact hypersensitivity, Graves’ disease, rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus, multiple sclerosis, psoriasis, and Behcet's disease. Here, we will review the biological characteristics of IL-37 and its key roles in various inflammatory and autoimmune diseases.
Shubhasree Banerjee; Kamel Hamzaoui; Anahid Safari; Afshin Borhani-Haghighi
Abstract
Neuro-Behcet's disease (NBD) is a rare but potentially fatal manifestation of Behcet's disease. Common presentations of neuro-Behcet's disease are parenchymal (brainstem and hemispheric manifestations, meningoencephalitis, spinal cord lesions) and non-parenchymal (arterial occlusions, aneurysms, Dural ...
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Neuro-Behcet's disease (NBD) is a rare but potentially fatal manifestation of Behcet's disease. Common presentations of neuro-Behcet's disease are parenchymal (brainstem and hemispheric manifestations, meningoencephalitis, spinal cord lesions) and non-parenchymal (arterial occlusions, aneurysms, Dural sinus thrombosis). Cerebrospinal fluid (CSF) findings in parenchymal NBD usually show an inflammatory pattern with elevated cell count (usually high levels of polymorphonuclear leukocytes), high protein, and normal glucose levels, whereas the CSF findings in non-parenchymal NBD could be normal except for high opening pressure. Further investigation of CSF in parenchymal NBD has demonstrated elevated Natural killer T cells, high inflammatory chemokines, and cytokines such as Tumor Necrosis Factor-alpha (TNF- α), Interferon-gamma (IFN-γ), Interleukin (IL)12, IL-6, IL-17, IL-26, IL-15, Vascular endothelial growth factor (VEGF), Matrix metallopeptidase 9 (MMP-9), chemokine [C-X-C motif] ligand 8 (CXC-8) which indicate the role of both innate and adaptive immunity in this disease. Particularly, T helper type 1 (TH-1) and TH-17 pathways are implicated in the pathogenesis of this condition. Successful use of certain biologic agents such as TNF and IL-6 inhibitors in NBD further emphasizes the role of inflammatory cytokines in the immunopathogenesis of the disease. Drugs blocking the TH 17 pathway such as ustekinumab, secukinumab could also be applicable in the process. This review summarizes the detailed CSF findings in NBD, current understanding of the immunopathogenesis of NBD, and treatment of NBD with specific biologic agents based on our understanding of the disease pathogenesis.
Hoorieh Soleimanjahi; Hadi Razavinikoo; Fatemeh Fotouhi; Abdollah Ardebili
Volume 14, Issue 3 , September 2017, , Pages 180-191
Abstract
Background: Vaccines based on virus-like particles are effective against Human Papilloma Virus (HPV) infection; however, they have not shown a therapeutic effect against HPV-associated diseases. New immunotherapy strategies based on immune responses against tumor antigens can positively affect the clearance ...
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Background: Vaccines based on virus-like particles are effective against Human Papilloma Virus (HPV) infection; however, they have not shown a therapeutic effect against HPV-associated diseases. New immunotherapy strategies based on immune responses against tumor antigens can positively affect the clearance of HPV-associated lesions. Objective: To generate two therapeutic fusion DNA vaccines (optimizedE7/mouseHSP70 and wildE7/mouseHSP70) to induce antitumor specific responses in mice models. Methods: Mice were immunized with recombinant DNA vaccines. The splenocytes of immunized mice were collected and lactate dehydrogenase and IFN-γ productions were measured after three injections in order to evaluate cytotoxic T lymphocytes (CTLs) activity. MTT assay was carried out for lymphocyte stimulation. Results: The fusion DNA vaccines, specifically uE7-HSP70, elicited varying levels of IFN-γ and CTLs responses compared to the control group (P<0.05). Furthermore, antitumor response and tumor size reduction in fusion DNA vaccines groups were significantly higher than in the negative control group (P<0.05). Conclusion: It is concluded that our fusion DNA vaccines considerably enhanced specific cellular responses against HPV tumor model. In addition, optimized E7 showed a notable immunogenicity and inhibitory effect on the reduction of tumor size.
Hossein Asgarian; Mahdi Shabani; Parvaneh Vosoogh; Ramazan Ali Sharifian; Soheila Gharagozlou; Jalal Khoshnoodi; Tahereh Shahrestani; Mahin Kordmahin; Abdolfattah Sarrafnejad; Mahmood Jeddi Tehrani; Hodjatallah Rabbani; Fazel Shokri
Volume 2, Issue 4 , December 2005, , Pages 182-190
Abstract
Background: The Wilm’s tumor gene 1 (WT1) encodes a zinc finger transcription factor that is inactivated in a subset of Wilm’s tumors. It plays a crucial role in growth, proliferation and development of some embryonic and adult organs. WT1 is expressed as a tumor associated antigen (TAA) ...
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Background: The Wilm’s tumor gene 1 (WT1) encodes a zinc finger transcription factor that is inactivated in a subset of Wilm’s tumors. It plays a crucial role in growth, proliferation and development of some embryonic and adult organs. WT1 is expressed as a tumor associated antigen (TAA) in various types of solid and hematopoietic malignancies and can be employed as a useful marker for targeted immunotherapy and monitoring of minimal residual disease (MRD). Objective: To investigate the profile of WT1 gene expression in Iranian patients with acute myeloblastic leukemia. Methods: RT-PCR method was used to determine the WT1 gene expression in bone marrow (BM) and/or peripheral blood (PB) samples from 11 patients with AML and PB samples of 36 normal subjects. Isolated cells from all patients were immunophenotyped by flow cytometry. Results: The leukemic cells from 10 patients (91%) were found moderately or strongly positive for WT1 expression whereas only 3 out of 36 normal subjects expressed WT1 at very low levels. A highly significant correlation was observed for WT1 expression between paired BM and PB samples of the AML patients. Conclusion: Our results indicate that WT1 is expressed in the majority of Iranian AML patients and may be employed for screening and monitoring of minimal residual disease in these patients.
Viroj Wiwanitkit
Volume 4, Issue 4 , December 2007, , Pages 186-196
Abstract
Mosquito borne infectious diseases are among important group of diseases worldwide. Vaccination is available for some tropical mosquito-borne diseases, especially for Japa-nese encephalitis virus infection and yellow fever. There are also several attempts to develop new vaccines for the other mosquito-borne ...
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Mosquito borne infectious diseases are among important group of diseases worldwide. Vaccination is available for some tropical mosquito-borne diseases, especially for Japa-nese encephalitis virus infection and yellow fever. There are also several attempts to develop new vaccines for the other mosquito-borne diseases such as malaria, dengue infection and West Nile virus infection. In this article, the author reviews the issues on vaccination of some important tropical mosquito borne infectious diseases.
Roya Payam Khaja Pasha; Fazel Shokri
Volume 5, Issue 4 , December 2008, , Pages 189-200
Abstract
RhD antigen is the most immunogenic and clinically significant antigen of red blood cells after ABO system. It has historically been associated with hemolytic disease of the newborn (HDN) which is now routinely prevented by the administration of polyclonal anti-D immunoglobulin. This management of HDN ...
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RhD antigen is the most immunogenic and clinically significant antigen of red blood cells after ABO system. It has historically been associated with hemolytic disease of the newborn (HDN) which is now routinely prevented by the administration of polyclonal anti-D immunoglobulin. This management of HDN has proven to be one of the most successful cases of prophylactic treatment based on antibody mediated immune sup-pression (AMIS). Despite the increasing efficiency of treatment, the mechanism of ac-tion of anti-D is not completely defined. There is a widespread interest in obtaining a reliable therapeutic monoclonal anti-D, due to difficulty of maintaining a pool of high titer volunteer donors for plasma collection and also increasing demand for antenatal prophylaxis and safety issues with plasma derived products. Candidate monoclonal anti-D preparations should demonstrate appropriate functionality in both in vitro and in vivo assays comparable to polyclonal anti-D immunoglobulin. These criteria are reviewed in addition to the factors regulating development of D specific immune response in D negative individuals and its suppression in HDN prophylaxis.
Enna Liu; Zheng Li; Yan Zhang; Kuisheng Chen
Abstract
Background: Macrophage polarization plays a critical role in determining the inflammatory states. Hepcidin is a key negative regulator of iron homeostasis and functions. Although hepcidin has been shown to affect ferroportin expression in macrophages, whether it affects macrophage polarization is still ...
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Background: Macrophage polarization plays a critical role in determining the inflammatory states. Hepcidin is a key negative regulator of iron homeostasis and functions. Although hepcidin has been shown to affect ferroportin expression in macrophages, whether it affects macrophage polarization is still largely unknown. Objective: To address whether hepcidin induces macrophage polarization. Methods: The expression of iNOS and CD206, and the ratio of IFN-γ vs IL-4 in THP-1 derived macrophages upon hepcidin stimulation were evaluated. Further detected was the percentage of CD16+ M1, CD23+ M1, CD10+ M2 and CCL22+ M2 cells in monocyte derived macrophages. Results: M1 associated molecules were increased in hepcidin-treated cells, yet M2 associated molecules were increased when hepcidin was neutralized. Concomitantly, we observed a significant increase in IRF3 phosphorylation in hepcidin-stimulated cells. However, STAT6 phosphorylation with hepcidin was neutralized. Conclusion: Hepcidin is able to induce macrophage polarization towards M1 type, and might be utilized as a potential M1 macrophage agonist in clinical practice.
Zahra Faghih; Somayeh Rezaeifard; Akbar Safaei; Abbas Ghaderi; Nasrollah Erfani
Volume 10, Issue 4 , December 2013, , Pages 193-204
Abstract
Background: CD8+ cytotoxic T lymphocytes have been recently divided based on their cytokine expression profile. Objective: To evaluate the percentages of CD8+ lymphocytes and their effector subsets including Tc1, Tc2 and Tc17 in the tumor draining lymph nodes (TDLNs) of patients with breast cancer. Methods: ...
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Background: CD8+ cytotoxic T lymphocytes have been recently divided based on their cytokine expression profile. Objective: To evaluate the percentages of CD8+ lymphocytes and their effector subsets including Tc1, Tc2 and Tc17 in the tumor draining lymph nodes (TDLNs) of patients with breast cancer. Methods: Single cell suspensions were obtained from TDLNs of 42 patients with breast cancer. Staining of the cell surface markers and intracellular cytokines was performed using appropriate fluorochrome-conjugated antibodies. The data was acquired on a four-color flow cytometer and was analyzed by CellQuestPro software package. The percentages of different CD8+ cell subtypes (Tc1, Tc2 and Tc17) were quantified in CD8+ T lymphocytes. The comparison was made between LN+ versus LN- patients, as well as patients in different clinico-pathological status. Results: The percentage of Tc1, Tc2 and Tc17 subsets were not significantly different between LN+ and LN- patients. Despite no difference in the percentages of Tc1 cells in LN+ patients with infiltrative ductal carcinoma (IDC), the mean expression of IFN-γ by Tc1 cells decreased significantly in comparison to LN- patients. On the other hand, the percentages of Tc2 and Tc17 effector subsets were increased in advanced stages (p=0.018 and p=0.009, respectively). Conclusion: As the first study to investigate various effector subtypes of CD8+ lymphocytes in TDLNs of patients with breast cancer, our data collectively suggests a positive association between IL-17- and IL-4-producing CD8+ T cell percentages (Tc2 and Tc17) in TDLNs with breast cancer progression. Although the number of Tc1 cells seems not to be affected by cancer progression, down-regulation of IFN-γ by these cells seems to be associated with tumor metastasis to TDLNs. These findings may have implications in cancer immunotherapy based on CD8+ effector subsets.
Mohammad Ali Ghayumi; Zahra Mojtahedi; Mohammad Javad Fattahi
Volume 8, Issue 4 , December 2011, , Pages 195-200
Abstract
Background: The alteration of Th1 and Th2 cytokine levels is the subject of controversy in pleural effusions caused by malignancy, a situation that favors a Th2 immune response. Objective: To examine the different levels of IL-4 and IL-10 (Th2 cytokines), and IL-2 and interferon-γ (IFN-γ) ...
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Background: The alteration of Th1 and Th2 cytokine levels is the subject of controversy in pleural effusions caused by malignancy, a situation that favors a Th2 immune response. Objective: To examine the different levels of IL-4 and IL-10 (Th2 cytokines), and IL-2 and interferon-γ (IFN-γ) (Th1 cytokines) in malignant and non-malignant pleural effusions. Method: The cytokine levels in pleural fluid of 62 patients with malignant pleural effusion (44 with lung cancer and 18 with extrathoracic tumors), 8 with tuberculous and 8 with congestive heart failure pleural effusion were analysed using enzymelinked immunosorbent assays. Results: IL-2 was below the detectable concentration of the assay. A significant decrease in IFN-γ level was observed in malignant but not in congestive heart failure cases compared to tuberculous cases. IL-10 levels were higher in malignant and tuberculous pleural effusions than in congestive heart failure pleural effusions, however, this difference did not reach the significant level. IL-4 levels were also increased non-significantly in lung cancer pleural effusions compared to the other groups. Conclusion: Our results show a wide variation in IL-4, IL-10, and IFN-γ levels in malignant pleural effusions, a pattern which was not convincing enough to differentiate the cause of effusion.
Rohollah Dorostkar; Taravat Bamdad; Masoud Parsania; Hassan Pouriayevali
Volume 9, Issue 4 , December 2012, , Pages 215-225
Abstract
Background: Improving vaccine potency in the induction of a strong cell-mediated cytotoxicity can enhance the efficacy of vaccines. Necrotic cells and the supernatant of necrotic tumor cells are attractive adjuvants, on account of their ability to recruit antigen-presenting cells to the site of antigen ...
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Background: Improving vaccine potency in the induction of a strong cell-mediated cytotoxicity can enhance the efficacy of vaccines. Necrotic cells and the supernatant of necrotic tumor cells are attractive adjuvants, on account of their ability to recruit antigen-presenting cells to the site of antigen synthesis as well as its ability to stimulate the maturation of dendritic cells. Objective: To evaluate the utility of supernatant of necrotic tumor cells as a DNA vaccine adjuvant in a murine model. Method: The supernatant of EL4 necrotic cells was co-administered with a DNA vaccine expressing the glycoprotein B of Herpes simplex virus-1 as an antigen model under the control of Cytomegalovirus promoter. C57BL/6 mice were vaccinated three times at two weeks intervals with glycoprotein B DNA vaccine and supernatant of necrotic EL4 cells. Five days after the last immunization, cell cytotoxicity, IFN-γ and IL-4 were evaluated. Results: The obtained data showed that the production of IFN-γ from the splenocytes after antigenic stimulation in the presence of the supernatant of necrotic EL4 cells was significantly higher than the other groups (p<0.002). The flow cytometry results showed a significant increase in the apoptosis/necrosis of EL4 cells in the mice immunized with DNA vaccine and supernatant of necrotic EL4 cells comparing to the other groups (p<0.001). Conclusion: The supernatant of necrotic cells contains adjuvant properties that can be considered as a candidate for tumor vaccination.
Atefeh Kamallou; Mahbobeh Haji Abdolbaghi; Minoo Mohraz; Mernaz Rasolinejad; Ehsan Karbasi; Bita Ansaripour; Samaneh Soltani; Arezou Rezaei; Neda Khalili; Aliakbar Amirzargar
Volume 11, Issue 4 , December 2014, , Pages 221-232
Abstract
Background: Lymphocyte subsets enumeration is considered prominent in the management of primary and acquired immunodeficiency disorders. Because of local variations due to race, age, gender, and environmental conditions on lymphocyte subsets, and to improve the accuracy of interpretation of laboratory ...
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Background: Lymphocyte subsets enumeration is considered prominent in the management of primary and acquired immunodeficiency disorders. Because of local variations due to race, age, gender, and environmental conditions on lymphocyte subsets, and to improve the accuracy of interpretation of laboratory findings, reference intervals must be determined in every population. Objective: To establish a normal reference range for CD3+ , CD4+ , CD8+ , CD19+ and CD56+ lymphocytes in a healthy Iranian adult population using flowcytometry. Method: Blood samples were collected from 221 HIV seronegative individuals, including 112 females and 109 males, with ages ranging from 20 to 40 years old. The percentage of lymphocytes expressing either of CD3, CD4, CD8, CD19 and CD56 surface markers were determined by flowcytometry assay. Result: Total mean percentage and absolute count of lymphocyte subsets were as follows: CD3+ : 70.90 ± 7.54%, 1800.87 ± 471.09 cells/µl; CD4+ : 41.04 ± 7.86%, 1039.99 ± 338.02 cells/µl; CD8+ : 31.11 ± 6.60%, 783.95 ± 234.87 cells/µl; CD19+ : 12.77 ± 4.56%, 328.37 ± 153.17 cells/µl; CD56+ : 15.53 ± 6.34%, 388.62 ± 176.17 cells/µl, respectively. The ratio of CD4+ /CD8+ lymphocytes for the studied population was 1.39 ± 0.48. Significant differences were observed between male and female subjects indicating that the average percentage of CD3+ cells (p=0.017) and CD4+ T cells (p=0.003) were higher in the female population, whereas the average percentage of CD19+ cells (p=0.02) tended to be higher among males. However, investigations on the CD56+ NK cell and CD8+ T cell sub-populations did not show any statistical differences between the two genders. In comparison with reports of other populations, we were confronted with different results. Conclusion: Establishing reference values of lymphocyte subsets for each population is helpful in achieving standard criteria for the prognosis of HIV infection. Therefore, normal ranges established by this survey can be used as a reference for decisions made in clinical practice.
Ladan Langroudi; Zuhair Muhammad Hassan; Masoud Soleimani; Seyed Mahmoud Hashemi
Volume 12, Issue 4 , December 2015, , Pages 226-239
Abstract
Background: Differentiation, 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. ...
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Background: Differentiation, 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. Objective: To characterize and compare the phenotype and cytokines of adipose derived MSCs (AD-MSCs) and tumoral-MSCs (T-MSCs) isolated from mammary tumors of BALB/c mice. Methods: Immunophenotyping and in vitro differentiation tests were used for MSC characterization. Cytokine and enzyme profiles were assessed using ELISA and Realtime PCR, respectively. Results: T-MSCs expressed significantly higher levels of HLADR (p=0.04). Higher levels of PGE2 and COX-2 enzyme were also observed in TMSCs (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). Conclusion: Functional differences showed by the surface markers of MSCs, cytokine and enzyme production indicate the effect of different microenvironments on MSCs phenotype and function.
Zahra Faghih; Saeideh Sadat Shobeiri; Ali Ariafar; Mohsen Sarkarian; Shahryar Zeighami; Nazanin Nazari; Saeed Abbasi-Sarvak; Nasrollah Erfani
Volume 13, Issue 4 , December 2016, , Pages 237-248
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 ...
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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.
Piyachat Evelyn Roopngam
Ahmad Mobed
Abstract
Tuberculosis (TB) is believed to be one of the leading causes of death in the world; nevertheless, Bacillus Calmette-Guérin (BCG) is the solitary vaccine utilized to prevent TB. Despite the protective effect of this vaccine in children, its efficiency remains under question in adults. We conducted ...
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Tuberculosis (TB) is believed to be one of the leading causes of death in the world; nevertheless, Bacillus Calmette-Guérin (BCG) is the solitary vaccine utilized to prevent TB. Despite the protective effect of this vaccine in children, its efficiency remains under question in adults. We conducted the present study to provide an overview of DNA based vaccines against TB and highlight the vaccine delivery advances and limitations. This study also aimed to bring a review of mycobacterial antigens, including heat shock protein 65 (Hsp65), antigen 85A (Ag85A), early secretory antigenic target 6 (EAST-6), antigen 85B (Ag85B), and heat shock protein X (HspX) as the most extensively considered antigens in the development of vaccines against M. tuberculosis.
Esmaeil Allahmoradi; Saeid Taghiloo; Mohsen Tehrani; Hadi Hossein-Nattaj; Ghasem Janbabaei; Ramin Shekarriz; Hossein Asgarian-Omran
Volume 14, Issue 4 , December 2017, , Pages 257-269
Abstract
Background: 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 ...
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Background: 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. Objective: To investigate the frequency and functional properties of exhausted CD4+ T lymphocytes in patients with CLL. Methods: 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. Results: 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. Conclusion: 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.
Samaneh Arab; Masoumeh Motamedi; Jamshid Hadjati
Abstract
Background: Dendritic cells (DCs) contribute essentially to the outset and course of immune responses. So in patients with malignancy, there have been considerable interests in use of these cells in different interventions. Objective: To evaluate the impact of Leishmania major’s components ...
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Background: Dendritic cells (DCs) contribute essentially to the outset and course of immune responses. So in patients with malignancy, there have been considerable interests in use of these cells in different interventions. Objective: To evaluate the impact of Leishmania major’s components on DC maturation and their use as a therapeutic agent against tumor cells. Methods: The cancer model was induced by injection of WEHI-164 cells (BALB/c derived fibrosarcoma cell line) subcutaneously in the right flank of animals. Bone-marrow derived DCs (BMDCs) were cultured with granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-4. After 5 days, tumor lysate, Leishmania major’s lysate, and Lipopolysaccharide (LPS) were added to the culture and incubated for 2 days. IL-12 production in DCs was measured by ELISA. For Immunotherapy, Mice received DCs subcutaneously around the tumor site. Two weeks after DCs injection, cytotoxicity assay and infiltration of CD8+ lymphocytes were evaluated. Results: Our results showed that immunotherapy with dendritic cells exposed to Leishmania extract led to producing a higher amount of IL-12, compare to the control group. A considerable increment in specific cytotoxic T cells activity, diminished tumor growth rate and improved survival of immunized animals were seen. Conclusion: This study indicates that the use of Leishmania major extract, as well as LPS, can enhance the efficiency of DC-based vaccines and provides a basis for the use of Leishmania major in DC-targeted clinical therapies.
Ali Shams; Sahar Khosravi; Aysan Zareiye; Yeganeh Lalehzari; Reyhane Nematollahi; Solmaz Basti
Abstract
Cell-mediated immunity (CMI) is crucial in controlling the highly aggressive and progressive SARS-CoV-2 infection. Despite extensive researches on severe COVID-19 infection, the etiology and/or mechanisms of lymphopenia, decreased T cell-mediated responses in patients, cytokine release storms (CRS), ...
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Cell-mediated immunity (CMI) is crucial in controlling the highly aggressive and progressive SARS-CoV-2 infection. Despite extensive researches on severe COVID-19 infection, the etiology and/or mechanisms of lymphopenia, decreased T cell-mediated responses in patients, cytokine release storms (CRS), and enhanced pro-inflammatory mediators are not fully understood. Several T cell subpopulations, including innate-like lymphocytes (ILLs) and conventional T cells, are involved in COVID-19 infection; however, their contribution to immunity and complications remains to be more elucidated. CD16+ T cells are among the effective players in the development of T helper1 (Th1) responses in COVID-19 infection, while their robust cytolytic properties contribute to lung tissue damage. While CD56-CD16bright NK cells play a protective role, natural killer T (NKT) cells, mucosal-associated invariant T (MAIT) cells, and γδ T cells and their roles in COVID-19 require further investigation. The involvement of the other T cell subsets, such as Th17, along with neutrophils, adds to the complexity of the situation. In this review, we presented and discussed the findings of recent studies on T cell responses and the contribution of each type of immune cells to COVID-19.
Farhad Shahsavar; Nader Tajik; Kobra-Zinat Entezami; Masoomeh Fallah Radjabzadeh; Behnam Asadifar; Kamran Alimoghaddam; Mohammadreza Ostadali Dahaghi; Arash Jalali; Andisheh Ghashghaie; Ardeshir Ghavamzadeh
Volume 7, Issue 1 , March 2010, , Pages 8-17
Abstract
Background: Interaction between killer cell immunoglobulin-like receptors (KIR) and human leukocyte antigen (HLA) class I molecules is important for regulation of natural killer (NK) cell function. Objective: The aim of this study was to investigate the impact of compound KIR-HLA genotype on susceptibility ...
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Background: Interaction between killer cell immunoglobulin-like receptors (KIR) and human leukocyte antigen (HLA) class I molecules is important for regulation of natural killer (NK) cell function. Objective: The aim of this study was to investigate the impact of compound KIR-HLA genotype on susceptibility to acute leukemia. Methods: Cohorts of Iranian patients with acute myeloid leukemia (AML; n=40) and acute lymphoid leukemia (ALL; n=38) were genotyped for seventeen KIR genes and their three major HLA class I ligand groups (C1, C2, Bw4) by a combined polymerase chain reaction–sequence-specific primers (PCR-SSP) assay. The results were compared with those of 200 healthy control individuals. Results: We found a significantly decreased frequency of KIR2DS3 in AML patients compared to control group (12.5% vs. 38%, odds ratio=0.23, p=0.0018). Also, the KIR3DS1 was less common in AML group than controls (27.5% vs. 44.5%, p=0.0465, not significant after correction). Other analyses including KIR genotypes, distribution and balance of inhibitory and activating KIR+HLA combinations, and co-inheritance of activating KIR genes with inhibitory KIR+HLA pairs were not significantly different between leukemia patients and the control group. However, in AML patients a trend toward less activating and more inhibitory KIR-HLA state was observed. Interestingly, this situation was not found in ALL patients and inhibition enhancement through increase of HLA ligands and inhibi-tory combinations was the main feature in this group. Conclusion: Our findings may suggest a mechanism for escape of leukemic cells from NK cell immunity.
Bijan Khademi; Marziyeh Tajvarpour; Zahra Mojtahedi; Mohammad Reza Haghshenas; Nasrollah Erfani
Volume 13, Issue 1 , March 2016, , Pages 9-15
Abstract
Background: Salivary gland tumors are among malignancies that have high recurrence rate. Immune responses in salivary gland tumors have not been well elucidated. T helper type 1 (Th1) and Th2 cytokines have been reported to play a role in the outcome of head and neck cancers. Objective: To evaluate the ...
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Background: Salivary gland tumors are among malignancies that have high recurrence rate. Immune responses in salivary gland tumors have not been well elucidated. T helper type 1 (Th1) and Th2 cytokines have been reported to play a role in the outcome of head and neck cancers. Objective: To evaluate the serum levels of interferon gamma (IFN- γ), as the hallmark of Th1 cytokines, and interleukin-4 (IL-4), as the hallmark of Th2 cytokines, in patients with benign and malignant salivary gland tumors in comparison with healthy controls. Methods: Fifty patients with benign and 14 patients with malignant salivary gland tumors, as well as 23 healthy individuals were recruited. Serum levels of IFN-γ and IL-4 were measured using ELISA method. Nonparametric tests were used for data analysis. Results: Serum levels of IFN-γ and IL-4 were found not to be significantly different in patients compared to the control group (0.68 ± 0.29 vs. 1.03 ± 0.57 pg/ml, p=0.58 for IFN-γ, 4.57 ± 1.57 vs. 4.41 ± 1.31 pg/ml, p=0.28 for IL-4). IFN-γ and IL-4 serum levels were also not significantly different between patients with benign and malignant salivary gland tumors (p=0.54 and p=0.86, respectively). Conclusion: The systemic levels of IL-4 and IFN-γ seem not to be associated with salivary gland tumor in our study. Investigation of other cytokines produced by Th1 and Th2 cells are warranted.
Minoo Adib; Fakhri Navaei; Farzad Oreizi; Fereshteh Saheb-Fosoul; Vajiheh Ostadi
Volume 3, Issue 1 , March 2006, , Pages 9-14
Abstract
Background: Neonatal sepsis is a life-threatening disease with an incidence of 1 to 10 per 1000 live births and a mortality rate of 15% to 50%. The clinical signs are non-specific and indistinguishable from those caused by a variety of neonatal noninfectious disorders. Objective: The aim of this study ...
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Background: Neonatal sepsis is a life-threatening disease with an incidence of 1 to 10 per 1000 live births and a mortality rate of 15% to 50%. The clinical signs are non-specific and indistinguishable from those caused by a variety of neonatal noninfectious disorders. Objective: The aim of this study was to determine the importance of CD64 expression (FcgRI), a neutrophil surface marker, in early diagnosis of neonatal sepsis. Methods: The studied population comprised of 65 neonates with gestational ages of 27 to 38 weeks, suspected of having sepsis in the first 28 days of life and 12 healthy neonates with physiologic hyperbilirubinemia. One ml of whole blood was obtained to determine CD64 expression on peripheral blood neutrophils by flow cytometry. Results: CD64 expression was significantly higher in the group with sepsis than the control groups (P < 0.001). Sensitivity and specificity of CD64 were 92.3% and 100%, respectively. The negative and positive predictive values of CD64 for identifying sepsis were 100% and 88%, respectively. Conclusion: A change in cell surface expression of CD64 on peripheral blood neutrophils may be considered as a sensitive marker for detection of neonatal sepsis if used in combination with other laboratory parameters.