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کاربرد نوع شرط:
- جایگاه : پژوهشی
- مجله: Iranian Journal of Immunology
- نوع مقاله: Journal Article
- کلمات کلیدی: Breast cancer,Adipose Derived Stem Cell (ASC),Naïve CD4+ T Cell,Regulatory T Cell,Tumor Microenvironment
- چکیده:
- چکیده انگلیسی: Background: Adipose derived stem cells (ASCs) provoke the accumulation and expansion of regulatory T cells, leading to the modulation of immune responses in tumor microenvironment.
Objective: To assess the effect of tumoral ASCs on the trend of regulatory T cells differentiation.
Methods: Peripheral blood naïve CD4+ T cells were co-cultured with ASCs derived from breast cancer or normal breast tissues. In separate cultures peripheral blood naïve CD4+ T cells were exposed to the culture supernatants of ASCs.
Results: Generation of CD4+CD25+Foxp3+ and CD4+CD25- Foxp3+ Treg subsets was observed after coculture of naïve CD4+ T cell with either ASCs or the related supernatant. The percentage of CD4+CD25+Foxp3+ cells increased after exposing naïve CD4+ T cells to both ASCs and their supernatants while augmentation of CD4+CD25-Foxp3+ subset mostly depended on the presence of ASCs. Similarly, upregulation of FoxP3 molecule was more significant in condition of cell to cell contact. IL-4 and IL-10 were up-regulated in the cocultured naïve CD4+ T cells after exposure to ASCs/supernatant while IFN-γ was down-regulated in the presence of ASCs.
Conclusion: Accordingly, ASC may act as one of the major players in tumor site with immunomodulatory effects, which may mostly be carried out through direct cellcell interaction.- انتشار مقاله: 14-05-1395
- نویسندگان: Mahboobeh Razmkhah,Nadieh Abedi,Ahmad Hosseini,Mohammad Taghi Imani,Abdol-Rasoul Talei,Abbas Ghaderi
- مشاهده
- جایگاه : پژوهشی
- مجله: Iranian Journal of Immunology
- نوع مقاله: Journal Article
- کلمات کلیدی: Breast cancer,Lymph node,Tc1,Tc2,Tc17
- چکیده:
- چکیده انگلیسی: 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.- انتشار مقاله: 15-05-1395
- نویسندگان: Zahra Faghih,Somayeh Rezaeifard,Akbar Safaei,Abbas Ghaderi,Nasrollah Erfani
- مشاهده
- جایگاه : پژوهشی
- مجله: Iranian Journal of Immunology
- نوع مقاله: Journal Article
- کلمات کلیدی: Squamous Cell Carcinoma,head and neck cancer,Polymorphism,CTLA-4,Haplotype,Genetic marker
- چکیده:
- چکیده انگلیسی: Background: Variations in Cytotoxic T Lymphocyte Antigen-4 (CTLA-4) affect the expression and function of this protein.
Objective: We aimed to investigate the association of +49 A/G (rs231775), +1822 C/T (rs231779) and +6230 A/G (CT60, rs3087243) genetic variations, as well as the merged haplotypes in CTLA-4 gene with susceptibility to, or progression of head and neck cancer.
Methods: Eighty patients with confirmed head and neck (HN) cancer (age 54.9 ± 16.1 years) and 85 healthy age/sexmatched controls (age 56.3 ± 12.4 years) were enrolled in the study. Genotypes were investigated by the PCR-RFLP method. Arlequin software package was used to check for Hardy-Weinberg equilibration, and to estimate the haplotypes.
Results: At position +6230 A/G (CT60), AA genotype, as well as A allele was significantly decreased in patients with HN cancers than controls (18.8% vs. 40.7%, p=0.004; odds ratio=0.34, and 46.3% vs. 61.7, p=0.007; odds ratio=0.53%, respectively). Nearly the same results were obtained when we compared the subgroup of patients with squamous cell carcinoma of the HN (SCC-HN) with control subjects. The frequencies of genotypes and alleles at other positions were not significantly different between patients and controls, however ACG, GTA and GCA haplotypes emerged from three investigated loci occurred with significantly more frequencies in patients (p<0.0001), while ACA and GTG haplotypes were more frequent among controls (p<0.0001). Significant differences of haplotypes, genotypes and alleles frequencies resisted the Bonferroni correction.
Conclusion: Our results suggest that CT60 A allele, as well as ACA and GTG haplotypes in CTLA-4 gene may have protective roles against HN cancer in Iranian population, while ACG, GTA and specially GCA haplotypes may render susceptibility.- انتشار مقاله: 15-05-1395
- نویسندگان: Nasrollah Erfani,Mohammad Reza Haghshenas,Mohammad Ali Hoseini,Seyed Basi Hashemi,Bijan Khademi,Abbas Ghaderi
- مشاهده
- جایگاه : پژوهشی
- مجله: Iranian Journal of Immunology
- نوع مقاله: Journal Article
- کلمات کلیدی: Breast cancer,Tumor,Polymorphism,Chemokine,Immunology,CCL22/MDC
- چکیده:
- چکیده انگلیسی: Background: CCL22/MDC is a CC chemokine with a critical role in regulation of the immune balance in physiological condition. CCL22/CCR-4 ligation has been documented to participate in the migration of regulatory T (Treg) cells and Th2 lymphocytes to the site of breast tumors; circumstances that are known to be associated with poor prognosis.
Objective: To investigate the association of a single nucleotide polymorphism (SNP) in CCL22 gene; 16C/A (rs4359426; Asp2Ala), with susceptibility to breast cancer in a sample of Iranian population.
Methods: 161 patients with pathologically confirmed breast carcinoma (mean age 49.3 ± 11.5 yrs) and 178 agematched healthy women (mean age: 49.3 ± 12.9 yrs) were studied. CCL22 genotypes were investigated by the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method. Data was verified by direct automated sequencing. Arlequin analysis showed no deviation from Hardy-Weinberg equilibrium.
Results: The most frequent genotype in both patient and control groups was wild type CC genotype with frequency of 146 out of 161 (90.7%) among patients and 153 out of 178 (86.0%) in control group (p=0.24). The frequency of CA genotype was 15 (9.3%) and 23 (12.9%) in patients and controls, respectively (p=0.38). No AA genotype was observed among patients but this genotype was observed with the frequency of 2 out of 178 (1.1%) in control subjects. The minor allele frequency (MAF) was 0.07 in the population.
Conclusion: No correlation was found between the investigated genotypes and clinicopathological characteristics of the patients. Conclusively, results of this investigation do not support the association of 16C/A SNP (rs4359426; Asp2Ala) in CCL22 gene with susceptibility to, and progression of, breast cancer in Iranian population.- انتشار مقاله: 15-05-1395
- نویسندگان: Nasrollah Erfani,Faezeh Moghaddasi-Sani,Mahboubeh Razmkhah,Mohammad Reza Haghshenas,Abdolrasoul Talaei,Abbas Ghaderi
- مشاهده
- جایگاه : پژوهشی
- مجله: Iranian Journal of Immunology
- نوع مقاله: Journal Article
- کلمات کلیدی: cancer,Polymorphism,autoimmunity,CTLA4,Immune Balance
- چکیده:
- چکیده انگلیسی: Gene association studies are less appealing in cancer compared to autoimmune diseases. Complexity, heterogeneity, variation in histological types, age at onset, short survival, and acute versus chronic conditions are cancer related factors which are different from an organ specific autoimmune disease, such as Grave’s disease, on which a large body of multicentre data is accumulated. For years the focus of attention was on diversity and polymorphism of major histocompatibility complex in respect to human diseases specially the autoimmune diseases, but in recent years, access to other human gene sequences prompted investigators to focus on genes encoding the immune regulatory proteins such as the co-stimulatory, adhesion molecules, cytokines and chemokines and their receptors. Among them, CTLA4 (CD152) has been in the centre of attention for its pivotal role in autoimmunity and cancer. Although not fully understood, CTLA4 with no doubt plays an important role in the maintenance of the immune response by its expression on activated and regulatory T cells. CTLA4 (Gene ID:1493, MIM number:123890) has many variants and polymorphic forms, some present in regulatory positions, some in 3' UTR and the most important one in the leader sequence (+49 A/G). As a pivotal regulatory element of the immune responses magnitude, CTLA4 could be considered as a two-blade knife, for which only the optimal expression ensures an effective, but at the same time, safe immune response. It can accordingly be speculated that CTLA4 alleles associated with extraordinary expression could make a person more susceptible to tumor growth and/or progression. On the other hand, alleles associated with a compromised CTLA4 expression/function may accelerate the formation and/or manifestation of inflammatory autoimmune disorder. I hypothesized a spectrum of the functional dichotomy of CTLA4 SNPs diverging from autoimmunity to cancer. To examine these hypotheses, results from previously published investigations on CTLA4 polymorphisms together with the work done by our own group are discussed in details. Because the most published data are about the polymorphism at position +49, I concentrated on this position; however the data regarding other SNPs are also included for comparison. To support the significance of CTLA4 gene variation in these two major human diseases evidences from organ transplantation are also included. As will be discussed in the manuscript, our work and reports by others from a normal population perspective support the hypothesis that individuals inheriting a GG genotype at position +49, for which lower CTLA4 expression has been extensively suggested, are more susceptible for developing autoimmune disorders and those with AA genotype, with an existence of a state of self-tolerance, may have a higher chance of developing cancer. CTLA4 SNPs may accordingly be considered as a crucial element, along with other known or yet unknown mechanisms, in keeping the immune balance in predisposed individuals to cancer and autoimmunity. Although an spectrum line can be drawn between autoimmunity and cancer by considering published data regarding CTLA4 +49 polymorphism, the extreme functional dichotomy of this SNP appears to be more complex and difficult to understand, but there is no doubt that the future investigations will resolve most ambiguities.
- انتشار مقاله: 16-05-1395
- نویسندگان: Abbas Ghaderi,Abbas Ghaderi,Abbas Ghaderi,Abbas Ghaderi
- مشاهده
- جایگاه : پژوهشی
- مجله: Iranian Journal of Immunology
- نوع مقاله: Journal Article
- کلمات کلیدی: Mesenchymal Stem Cells,Jurkat cells,Suppression
- چکیده:
- چکیده انگلیسی: Background: Several studies have demonstrated the immunosuppresive effects of mes-enchymal stem cells (MSCs) in allogeneic or mitogenic interactions. Cell-cell contact inhibition and secretion of suppressive soluble factors have been suggested in this re-gard.
Objective: To investigate if adipose derived MSCs could inhibit Jurkat lym-phoblastic leukemia T cell proliferation during coculture.
Methods: Adherent cells with the ability of cellular growth were isolated from normal adipose tissues. Initial charac-terization of growing cells by flow cytometry suggested their mesenchymal stem cell characteristics. Cells were maintained in culture and used during third to fifth culture passages. Jurkat or allogeneic peripheral blood mononuclear cells (PBMCs) were la-beled with carboxy fluorescein diacetate succinimidyl ester and cocultured with increas-ing doses of MSCs or MSC culture supernatant. Proliferation of PBMCs or Jurkat cells under these conditions was assessed by flow cytometry after 2 and 3 days of coculture, respectively.
Results: Results showed the expression of CD105, CD166 and CD44, and the absence of CD45, CD34 and CD14 on the surface of MSC like cells. Moreover, ini-tial differentiation studies showed the potential of cell differentiation into hepatocytes. Comparison of Jurkat cell proliferation in the presence and absence of MSCs showed no significant difference, with 70% of cells displaying signs of at least one cell division. Similarly, the highest concentration of MSC culture supernatant (50% vol/vol) had no significant effect on Jurkat cell proliferation (p>0.6). The same MSC lots significantly suppressed the allogeneic PHA activated PBMCs under similar culture conditions.
Conclusion: Using Jurkat cells as a model of leukemia T cells, our results indicated an uncertainty about the suppressive effect of MSCs and their inhibitory metabolites on tumor or leukemia cell proliferation. Additional systematic studies with MSCs of differ-ent sources are needed to fully characterize the immunological properties of MSCs be-fore planning clinical applications.- انتشار مقاله: 16-05-1395
- نویسندگان: Neda Mousavi Niri,Mansooreh Jaberipour,Mahboobeh Razmkhah,Abbas Ghaderi,Mojtaba Habibagahi
- مشاهده
- جایگاه : پژوهشی
- مجله: Iranian Journal of Immunology
- نوع مقاله: Journal Article
- کلمات کلیدی: NSCLC,ME3D11,Mehr-80
- چکیده:
- چکیده انگلیسی: Background: Lung carcinoma is a multiple type cancer comprising of small cell and non-small cell carcinomas (NSCLC). For therapeutic and diagnostic purposes, serum monoclonal antibodies have been produced against lung cancer.
Objective: To charac-terize a murine monoclonal antibody (ME3D11) reactive with human NSCLC.
Methods: A murine monoclonal antibody (ME3D11) reactive with human NSCLC was selected after immunization of BALB/c mice with a human large cell carcinoma with neuroen-docrine differentiation, and was tested by immunofloursence staining and Western blot analysis.
Results: Our study showed that the antigen recognized by ME3D11 antibody was a cell surface antigen of 170kDa. This antigen is expressed on the cell surface of all NSCLC and a few carcinoma cell lines. In contrast, this antigen is neither expressed on the cell surface of human sarcoma, nor on the hematopoietic and normal cell lines. This anti-body had no effect on spontaneous proliferation of Mehr-80 cell line in vitro.
Conclusion: High degree of binding of this monoclonal antibody to NSCLC and some other carci-noma cells warrants further studies on its potential use in diagnosis and therapy of can-cer by conjugation to drugs, toxins or radionuclides.- انتشار مقاله: 17-05-1395
- نویسندگان: Sedigheh Sharifzadeh,Helmout Modjtahedi,Mahmood Jedi Tehrani,Abbas Ghaderi
- مشاهده
- جایگاه : پژوهشی
- مجله: Iranian Journal of Immunology
- نوع مقاله: Journal Article
- کلمات کلیدی: Iran,HLA polymorphism,Arabs,Jews
- چکیده:
- چکیده انگلیسی: Background: Anthropological studies based on highly polymorphic HLA genes pro-vide useful information for bone marrow donor registry, forensic medicine, disease as-sociation studies, as well as designing peptide vaccines against tumors, and infectious or autoimmune diseases.
Objective: This study was designed to investigate the genetic relationship of Iranian Arabs and Jews using HLA-class II genetic diversity
Methods: HLA-DRB1, DQA1, and DQB1 allele frequencies and haplotypes were determined in 134 Iranian Arabs from two different communities and 91 Iranian Jews using PCR/RFLP and PCR/SSP methods.
Results: Neighbor-joining analyses showed a closer genetic relationship between Iranian Arabs and Iranian Jews than between either Iranian Arabs and Middle Eastern Arabs or Iranian Jews and other Jews. The results of AMOVA test also revealed no significant difference between these populations and other Iranians.
Conclusion: It seems that, Iranian Arabs are originally from the Iranian gene pool and speak Arabic due to their encounter with Arabs. Iranian gene flow to im-migrant Jews followed by their expansion in this country may also explain the close ge-netic relationship among different Iranian ethnic groups.- انتشار مقاله: 17-05-1395
- نویسندگان: Shirin Farjadian,Abbas Ghaderi
- مشاهده
- جایگاه : پژوهشی
- مجله: Iranian Journal of Immunology
- نوع مقاله: Journal Article
- کلمات کلیدی: IgG,Lymphocytes,IgA,IgM,Tonsil
- چکیده:
- چکیده انگلیسی: Background: Tonsils and adenoids are involved in both local immunity and immune surveillance for the development of immune defense mechanisms. A number of investigators have found decreased immunoglobulin levels after adenotonsillectomy while others have failed to find significant changes. The effects of adenotonsillectomy on the cellular immunity of children have not been investigated extensively.
Objective: To observe the change in humeral and cellular immune systems before and after operation in patients undergoing adenotonsillectomy.
Methods: The study comprised 102 patients; all of the patients underwent adenotonsillectomy. The levels of IgG, IgA, and IgM were measured for humoral immunity and the percent of CD7 and CD19 positive cells were determined in blood samples taken from these patients 24 hours before operation and also 2 and 8 weeks after the operation. The results were subjected to statistical analysis.
Results: The present study shows that the serum level of IgA would rise few weeks after the operation. Changes in the IgM and IgG level were not statistically significant postoperatively. In addition, no significant change was detected in B lymphocyte count before and after adenotonsillectomy. In our study, there was a slight decrease in the T lymphocyte count in the early stage of post operation, which returned to normal preoperative value after 8 weeks .
Conclusion: Several immune system parameters maintain its normal status several weeks after adenotonsillectomy.- انتشار مقاله: 16-05-1395
- نویسندگان: Abolhassan Faramarzi,Azra Shamsdin,Abbas Ghaderi
- مشاهده
- جایگاه : پژوهشی
- مجله: Iranian Journal of Immunology
- نوع مقاله: Journal Article
- کلمات کلیدی: Iran,Anthropology,HLA polymorphism,Lurs
- چکیده:
- چکیده انگلیسی: Background: HLA genes are highly polymorphic and certain alleles are frequent only in specific populations. Therefore, HLA is a unique tool for studying the genetic relationship between different populations. Iranians are ethnically diverse people and one of the major ethnic groups in Iran is Lur population inhabiting along the central and southern parts of Zagros Chain Mountain.
Objectives: Genetic relationship among three Lur subpopulations was investigated based on HLA class II profiles.
Methods: HLA typing was performed using PCR/RFLP and PCR/SSP methods in 154 individuals from three Lur subpopulation living in Luristan, Kohkiloyeh/ Boyerahmad, and Chahar-Mahal/ Bakhtiari.
Results: The most common DRB1 allele in Lurs of Luristan and Kohkiloyeh/ Boyerahmad was *1103=4 while DRB1*0701 was the most common allele in Bakhtiaris. DQA1*0501 and DQB1*0301 were the most frequent alleles and DRB1*1103=04-DQA1*0501-DQB1*0301 was the predominant haplotype in the three studied subpopulations. Neighbor-joining tree based on Nei's genetic distances and correspondence analysis according to DRB1, DQA1, and DQB1 allele frequencies showed a close genetic relationship between Lurs of Luristan and Lurs of Kohkiloye/ Boyerahmad and they were well separated from Bakhtiaris. The results of AMOVA revealed no significant difference between the three studied groups of Lurs and other major ethnic groups of Iran.
Conclusion: The results of this study revealed that Bakhtiaris were genetically far from the two other Lur subpopulations. Despite a probable common ancestor, this genetic difference might be explained by Bakhtiaris admixture with other Zagros inhabitants due to their nomadic life style.- انتشار مقاله: 16-05-1395
- نویسندگان: Shirin Farjadian,Abbas Ghaderi
- مشاهده