Drug hypersensitivity involves the activation of T cells in an HLA allele–restricted manner. Because the majority of individuals who carry HLA risk alleles do not develop hypersensitivity, other parameters must control development of the drug-specific T cell response. Thus, we have used a T cell–priming assay and nitroso sulfamethoxazole (SMX-NO) as a model Ag to investigate the activation of specific TCR Vβ subtypes, the impact of programmed death -1 (PD-1), CTL-associated protein 4 (CTLA4), and T cell Ig and mucin domain protein-3 (TIM-3) coinhibitory signaling on activation of naive and memory T cells, and the ability of regulatory T cells (Tregs) to prevent responses. An expansion of the TCR repertoire was observed for nine Vβ subtypes, whereas spectratyping revealed that SMX-NO–specific T cell responses are controlled by public TCRs present in all individuals alongside private TCR repertoires specific to each individual. We proceeded to evaluate the extent to which the activation of these TCR Vβ–restricted Ag-specific T cell responses is governed by regulatory signals. Blockade of PD-L1/CTLA4 signaling dampened activation of SMX-NO–specific naive and memory T cells, whereas blockade of TIM-3 produced no effect. Programmed death-1, CTLA4, and TIM-3 displayed discrete expression profiles during drug-induced T cell activation, and expression of each receptor was enhanced on dividing T cells. Because these receptors are also expressed on Tregs, Treg-mediated suppression of SMX-NO–induced T cell activation was investigated. Tregs significantly dampened the priming of T cells. In conclusion, our findings demonstrate that distinct TCR Vβ subtypes, dysregulation of coinhibitory signaling pathways, and dysfunctional Tregs may influence predisposition to hypersensitivity.
Background: Diabetes is a metabolic disorder characterized by chronic hyperglycemia due to an inability to produce insulin. Uncontrolled or poorly controlled diabetes is clinically associated with increased susceptibility to delay healing. Many recent researches have shown that stem cell therapy can be the best choice for treatment of this disease. The aims of this research were investigating regeneration of pancreatic beta cells of diabetic induced rabbits after stem cell transplantation. Materials and Methods: 64 rabbits weighting an average of (2.5 - 3 kg) were used in this experimental study, and divided into 4 groups as follows; group A ( contains 16 healthy rabbits regarded as control group ) , Group B ( contains 16 diabetic rabbits
... Show MoreAryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a potent ligand for AhR and a known carcinogen. While AhR activation by TCDD leads to significant immunosuppression, how this translates into carcinogenic signal is unclear. Recently, we demonstrated that activation of AhR by TCDD in naïve C57BL6 mice leads to massive induction of myeloid derived-suppressor cells (MDSCs). In the current study, we investigated the role of the gut microbiota in TCDD-mediated MDSC induction. TCDD caused significant alterations in the gut microbiome, such as increases in Prevotella and Lactobacillus, while decreasing Sutterella and Bacteroides. Fecal transplants from TCDD-treated
... Show MoreBackground: The anticancer impact of Epigallocatechin gallate (EGCG) the highly active polyphenol of green tea was abundantly studied. Though, the exact mechanism of its cytotoxicity is still under investigation. Objectives: Hence, the current study designed to investigate the molecular target of EGCG in HepG2 cells on thirteen autophagy- and/or apoptosis- related genes. Methods: The apoptosis detection analyses such as flow cytometry and dual apoptosis assay were used. The genes expression profile was explored by the real-time quantitative-PCR. Results: EGCG increases G0/G1 cell cycle arrest and the real-time apoptosis markers proteins leading to stimulate apoptos
... Show MoreCancer stem cells (CSCs) are defined as a population of cells present in tumours, which can undergo self-renewal and differentiation. Identification and isolation of these CSCs using putative surface markers have been a priority of research in cancer. With this background we selected pancreatic normal and tumor cells for this study and passaged them into animal tissue culture medium. Further staining was done using alkaline phosphatase and heamatoxilin staining. Blue to purple colored zones in undifferentiated pluripotent stem cells and clear coloration in the chromatin material indicated pancreatic cells. Further studies on the cell surface marker CD 44 were done using ELISA. For this, the protein was extracted from cultivated normal and t
... Show MoreLasers has been proved to increase tissue oxygenation, activate marrow progenitor cells, expanse the microcirculation, accelerate the restoration of functions, stimulate adaptation ability and stabilization of the hormonal status. The semisolid tissue present in the epiphysis of the bone where it’s structure is spongy or cancellous is bone marrow and it formed about 4% of body weight, the marrow is composed of hemopoietic cells, however, the structure of the marrow is of both cellular and non – cellular components. The hemopoietic stem cells are responsible of producing white blood cells, red corpuscles, platelets in addition to the fibroblasts, macrophages, adipocytes, osteoblast
In this research The study of Multi-level model (partial pooling model) we consider The partial pooling model which is one Multi-level models and one of the Most important models and extensive use and application in the analysis of the data .This Model characterized by the fact that the treatments take hierarchical or structural Form, in this partial pooling models, Full Maximum likelihood FML was used to estimated parameters of partial pooling models (fixed and random ), comparison between the preference of these Models, The application was on the Suspended Dust data in Iraq, The data were for four and a half years .Eight stations were selected randomly among the stations in Iraq. We use Akaik′s Informa
... Show MoreIn this research The study of Multi-level model (partial pooling model) we consider The partial pooling model which is one Multi-level models and one of the Most important models and extensive use and application in the analysis of the data .This Model characterized by the fact that the treatments take hierarchical or structural Form, in this partial pooling models, Full Maximum likelihood FML was used to estimated parameters of partial pooling models (fixed and random ), comparison between the preference of these Models, The application was on the Suspended Dust data in Iraq, The data were for four and a half years .Eight stations were selected randomly among the stations in Iraq. We use Akaik′s Informa
... Show MoreWe study in this paper the composition operator that is induced by ?(z) = sz + t. We give a characterization of the adjoint of composiotion operators generated by self-maps of the unit ball of form ?(z) = sz + t for which |s|?1, |t|<1 and |s|+|t|?1. In fact we prove that the adjoint is a product of toeplitz operators and composition operator. Also, we have studied the compactness of C? and give some other partial results.
This study examines the factors that affect oral participation of six Arab postgraduate students (two Iraqis, two Jordanians, and two Libyans), namely, three male participants and three female participants. For this purpose, a semi-structured interview was employed. The results showed that female as well male interviewees share some factors that make oral participation in classroom disheartening. These factors include high levels of anxiety, lack of confidence, shyness, and lack of preparation. It was also that there is no difference between male and female interviewees in relation to the factors that make them feel disheartened from oral classroom participation.