Background: Regulatory CD4+Foxp3+T cells (Tregs) play an important role in the prevention of autoimmune disease. It is also suggested that in multiple sclerosis (MS), a central nervous system disease, an aberrant Treg function may play a role. LYMPHOCYTE ACTIVATION GENE3 ((LAG-3)) as a surface marker of Treg cells with negative regulation of the immune system can effectively encounter with effector LYMPHOCYTEs. In this study, we evaluated frequency of CD4+Foxp3+(LAG-3)+T cells before and after treatment with Fingolimod.Methods: Blood samples was obtained from 20 patients with multiple sclerosis before and after 1 months of Fingolimod treatment, and from 12 age-matched healthy control subjects. Then pripheral blood mononuclear cell (PBMCs) were isolated and the frequency of Treg cells expressing (LAG-3) were determined by flowcytometry.Findings: The frequency of CD4+Foxp3+LAG3+T cells in the peripheral blood of MS patients was increased when compared to baseline (P=0.005).Conclusion: Our findings suggested that Fingolimod not only increases CD4+Foxp3+Treg cells, but also is able to enhance expression of (LAG-3) on their surface. This is a new finding for the Fingolimod on the immune system.

Background: Rheumatoid arthritis (RA) is described as a systemic and chronic autoimmune disease characterized by inflammatory polyarthritis. LYMPHOCYTEACTIVATION GENE 3 (LAG3) is a membrane glycoprotein expressed on activated, exhausted, and regulatory T cells. LAG3 plays a major role in the function of Treg cells. LAG3 also has a soluble form (sLAG3) with a controversial role. Objective: To evaluate the serum level of sLAG3 in rheumatoid arthritis patients in comparison with healthy subjects and assess its association with the disease activity. Methods: This cross-sectional study was performed on 105 patients with RA referred to Ghaem hospital of Mashhad, Iran. We divided the participants into four groups: 1) 35 untreated patients with newly diagnosed RA, 2) 35 active RA patients, 3) 35 patients in the remission phase of the disease, and 4) 35 healthy individuals matched in terms of age and sex. After completing the interview and questionnaire, the sLAG3 was evaluated by commercial ELISA. Results: The serum level of sLAG3 significantly increased in RA patients (76. 78 ng/ml) as compared with the healthy participants (51. 67, p=0. 002). However, there was no significant difference between RA patients in the remission phase of the disease (114. 11 ng/ml) and those with moderate to high disease activity (63. 06 ng/ml, p=0. 076). Conclusion: This study provided insights into the role of sLAG3 in the immunopathoGENEsis of RA disease, but further investigations are also warranted.

Background: Tuberculosis is still a major health problem around the globe. Better knowledge of different aspects of the disease, including immunology and immuno- pathoGENEsis, promises better control measures. Studies regarding quantitative and qualitative changes of LYMPHOCYTEs have developed our knowledge to a great extent. In this study, quantitative deficiencies of LYMPHOCYTE sub-populations and their ACTIVATION markers have been evaluated.Materials and Methods: Following documentation of smear positive pulmonary Tuberculosis in adult patients referred to Massih Daneshvari Hospital, 40 new cases without any other immunodeficiency conditions such as HIV, CRF, etc were randomly selected. Tuberculin skin test (TST) and chest radiography were performed for each case, and flow-cytometry was done from peripheral blood for LYMPHOCYTE sub-populations as CD3, CD4, CD8, CD4/CD8 ratio, CD19, CD16+56, and for LYMPHOCYTE ACTIVATION markers including CD25, CD69 and HLA-DR. Comparison was made with the historical control group" in a study in same city, age as well as same flow -cytometry operator and same including & excluding criteria. Statistical analysis of data using Spearman's rho, Mann- Whitney U, and Asymp. Sig. (2-tailed) was done.Results: 18 cases (45%) were male and 22 (55%) were female .Age distribution had a minimum of 17 and a maximum of 80 with a mean of 44.18 (19.65). Considering flow-cytometric marker correlation's, HLA-DR had significant relation to age (P=0.002). The ratio of CD4+ cells also had significant relation to CD3, CD16+56 and HLA-DR markers. A significant difference was found only in the total of CD3+ LYMPHOCYTEs by comparing PPD positive cases (>or =10 mm)with PPD negative patients. The ratio of CD4+ was significantly lower than the normal population, and CD8+ was significantly higher comparing to the control population. The CD4/CD8 ratio was also significantly lower than the normal population.Conclusion: Expression of LYMPHOCYTE sub-populations during the course of pulmonary Tuberculosis disease showed positive or negative correlation. By comparing LYMPHOCYTE sub-populations of TB patients with the control group, it is concluded that CD4+, CD8+, and CD4/CD8 ratio show significant differences that confirm significant quantitative defects in LYMPHOCYTEs due to tuberculosis disease.

Silver nanoparticles (Ag-NPs) are among the most widely used nanomaterials in the world. Nanotoxicological data on these additives remain unclear. The aim of this study is to evaluate the in vivo effects of Ag-NPs bioaccumulation on the hematological cells of adult zebrafish Danio rerio after three weeks of oral exposure. Four concentrations of Ag-NPs (65 nm nanosphere), are used: control group 1 (0. 00 g/kg of food), group 2 (0. 05 g/kg of food), group 3 (5 g/kg of food) and group 4 (50 g/kg of food). The experiment is conducted in triplicate. Cytological and histological results show, a significant increase in neutrophils associated with a significant decrease in LYMPHOCYTEs in both group 3 and 4 compared to the control group (p<0, 05 and p<0, 005, respectively). This reflects an elevated neutrophil/LYMPHOCYTE ratio (NLR), suggesting a biased immune response associated with hyperplasia of the hematopoietic tissue and histopathological images of nephrological lesions, following medium to high dose of Ag-NPs intake. Besides, microscopic observation of cell morphology revealed LYMPHOCYTE ACTIVATION only in groups 2 and 3 (p<0, 005 and p<0, 05, respectively). These results suggest that Ag-NPs induce a dose-dependent bioeffects on the immune system in zebrafish. This study reports that at low doses, Ag-NPs may activate LYMPHOCYTEs but do not alter the NLR, thus demonstrating an immunostimulatory effect. The present investigation is the first study, as far as we know, reporting that Ag-NPs induce a dose-dependent immunomodulation in zebrafish

Introduction: Tuberculosis is still a major health problem around the world Should we get better knowledge of different aspects of the disease, including immunology and immuno-pathoGENEsis, we can take better control measures. Studies regarding the quantitative and qualitative changes of LYMPHOCYTEs have increased our knowledge to a great extent. In these study quantitative deficiencies of LYMPHOCYTE sub-populations and their ACTIVATION markers have been investigated.Materials & Methods: Following documentation of smear positive pulmonary Tuberculosis in adult patients referred to Massih Daneshvari Hospital, 40 new cases without any other immunodeficiency conditions such as HIV, CRF, etc. were randomly selected. Tuberculin skin test (TST) and chest radiography were performed for each case, and flow-cytometry was done from peripheral blood for LYMPHOCYTE sub-populations as CD3, CD4, CD4/CD8 ratio, CD19, CD16+56, and for LYMPHOCYTE ACTIVATION markers including CD25, CD69 and HLA-DR. Comparisons were made for the historical control group with same age flow-cytometry operator and including & excluding criteria. Statistical analysis was done using Spearman's rho, Mann-Whitney U, and Asymp Sig (in a study in the same city, 2-tailed). Results: 18 cases (45%) were male and 22 (55%) were female. Age distribution had a minimum of 17 and a maximum of 80 with a mean of 44.18 (19.65). Considering flow-cytometric marker correlations, HLA-DR had significant relation with age (p=0.002). The ratio of CD4+ cells also had significant relation with CD3, CD16+56 and HLA-DR markers. A significant difference was found only in the total of CD3+ LYMPHOCYTEs by comparing PPD positive cases (>or =10mm) to PPD negative patients. The ratio of CD4+cells also was significantly lower than the normal population; however, CD8+ was significantly higher compared to the control population. The CD4/CD8 ratio was also significantly lower than the normal population. Conclusion: The expression of LYMPHOCYTE sub-populations during the course of pulmonary Tuberculosis disease showed positive or to negative correlation. By comparing LYMPHOCYTE sub-populations of TB patients the control group, it can be concluded that CD4+, CD8+, and CD4/CD ratio show significant differences that confirm significant quantitative defects in LYMPHOCYTEs due to tuberculosis disease.

Aims The correlation between high levels of blood lipid with the induction of some diseases indicates significant effects of hyperlipidemia and especially hypercholesterolemia on the immune system, inflammatory response, and secretion of cytokines. This is due to changes in the composition of cholesterol in the cell membrane and macrophage cytoplasm, which disrupts the signaling pathway necessary for the innate immune response. The purpose of this study was to investigate the effect of hypercholesterolemia on phenotype properties of T cells and the expression of its associated ACTIVATION markers. Materials & Methods In the present experimental study 3ml of peripheral blood samples were collected from 30 hypercholesterolemia patients and 30 healthy subjects. The distribution of ACTIVATION markers was evaluated by Immunophenotyping with anti-CD4, CD8, CD25, and CD69 antibodies. T independent test was used and output data were analyzed using Flow Jo 10 and SPSS 16 software. Findings Evaluation of the ACTIVATION markers located on T cells of patients with hypercholesterolemia showed a significant decline by 0. 8% and 2% in the expression of CD25 marker and 1. 92% and 2. 12% in the expression of CD69 marker on CD8+ and CD4+ T cells, respectively (p<0. 05). Conclusion The changes in the phenotype properties of T cells and the decreased expression of ACTIVATION markers in high-level cholesterol conditions might weaken the immune system in hyperlipidemia patients.

Background: Similar to inflammatory cells, peripheral blood mononuclear cells (PBMCs) can also infiltrate in to kidney and urinary tracts and subsequently excreted by urine. In this study we determined the viability rate and response to phytohemagglutinin-A (PHA) of human PBMCs in normal urine.Methods: A number of 1×106 ficoll-hypaque isolated PBMCs were dispensed in 1 ml normal urine and 6 molar urea and RPMI-1640+FBS10 % were considered as negative and positive control, respectively. After 20, 60 and 120 minutes the viability of these cells was measured by trypan blue dye exclusion assay. 1×105 of PBMCs were isolated from urine and cultured as triplicate in RPMI-1640 supplemented with FBS 10% and PHA for 96hr. MTT assay was performed to determine the PBMCs response to PHA. These experiments were repeated three times independently.Results: There was no significant difference between the viability rates of the PBMCs incubated in urine and positive control after 20, 60 and 120 minutes while after 60 minutes they exhibited 75.6% of reactivity to PHA versus positive control. Overall, there was a significant difference in trends of viability rate across the three groups (p<0.05).Conclusion: Our results showed that not only PBMCs remained alive in urine after 120 minutes, but can also respond to PHA up to 60 minutes at a remarkable level. These data open a new avenue in the designation for cell culture-based techniques in urine cell analysis.