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.
Abstract
Heavy-duty diesel vehicle idling consumes fossil fuel and reduces atmospheric quality at idle period, but its restriction cannot simply be proscribed. A comprehensive tailpipe emissions database to describe idling impacts is not yet available. This paper presents a substantial data set that incorporates results from DI multi-cylinders Fiat diesel engine. Idle emissions of CO, hydrocarbon (HC), oxides of nitrogen (NOx), smoke opacity, carbon dioxide (CO2) and noise have been reported, when three EGR ratios (10, 20 and 30%) were added to suction manifold.
CO2 concentrations increased with increasing idle time and engine idle speed, but it didn’t show clear effect for IT adva
... Show MoreThis research involves study effect of chloride ions in concentration range (0.01 – 0.50 mol.dm-3) on the corrosion behavior of Al-Zn alloy in basic media of 1x10-3 mol.dm-3 NaOH at pH=11 and four different temperatures in the range (298-313 K). Cathodic and anodic Tafel slopes (bc &ba) and transfer coefficients (αc & αa) were calculated and the results interprets according to the variation of the rate – determining steps. The results also indicate that the chloride ions are bonded chemically in the interface as an initial step of formation of different mixed oxohydroxy – and chloro complexes. Polarization resistance (Rp) is calculates
... Show MorePVC/Kaolinite composites were prepared by the melt intercalation method. Mechanical properties, thermal properties, flammability and water absorption percentage of prepared samples were tested. Mechanical characteristic such as tensile strength, elongation at break; hardness and impact strength (charpy type) were measured for all samples. It was found that the tensile strength and elongation at break of PVC composites decreased with increasing kaolinite loading. Also, the hardness of the composites increases with increase in filler content .The impact strength of the composites at the beginning increases at lower kaolinite loadings is due to the lack of kaolin adhesion to the matrix. However, at higher kaolin loadings. This severe agglom
... Show MoreBackground: Polymethyl methacrylate (PMMA) is used in denture fabrication and considered as the most reliable material for the construction of removable prosthodontic appliances. The material is far from ideal in fulfilling the mechanical requirements and the effect of autoclave processing has not been fully determined. The purpose of this study was to evaluate the effect of addition of salinized (ZrO2) Nano fillers in percentages 3%, 5% and 7% by weight on some properties of heat cured acrylic processed the by autoclave and compare it with 0% (control) group . Materials and methods: The silanized(ZrO2) Nano-particles was added to PMMA powder by weight in three different percentages 3%, 5% and 7%, mixed by probe ultra-sonication machine.
... Show MoreFocusing on the negative role of default risk on banks, as it is one of the most important risks facing banks, which are difficult to determine accurately, and its reflection on the indicators of profitability of cash flows. The increasing competition between banks led to an increase in the credit facilities granted by banks, and was accompanied by an increase in exposure to the risks of default, which led to an impact on the level of performance of banks in terms of achieving the required return according to the levels of high competition. Therefore, the problem of this study focused on the extent to which the risk indicators of default affect the profitability indicators of the cash flows of the banks research sample in the profit
... Show MoreThe effect of time (or corrosion products formation) on corrosion rates of carbon steel pipe in aerated 0.1N NaCl
solution under turbulent flow conditions is investigated. Tests are conducted using electrochemical polarization
technique by determining the limiting current density of oxygen reduction in Reynolds number range of 15000 to 110000
and temperature range of 30 to 60oC. The effect of corrosion products formation on the friction factor is studied and
discussed. Corrosion process is analyzed as a mass transfer operation and the mass transfer theory is employed to
express the corrosion rate. The results are compared with many proposed models particularly those based on the
concept of analogy among momentum, heat,
Background: Fluoridated acrylic resin material can present more stable properties when compared with conventional one.The most widely used fluoride –containing substance added to dental resin materials is sodium fluoride (Naf). This study evaluated the effect of Naf in different concentration to the acrylic resin denture base material and its effect on tensile strength ,modules of elasticity with long –term water immersion (after 4 months immersion in de-ionized water) Materials and methods: Eighty specimens from dumbbells shaped metal pattern for tensile strength test were preparedaccording to ISO 527: 1993 plastic –Determination tensile properties ,in dimensions(60mm, 12mm, 3 ± 0.2mm) length, width and depth respec
... Show MoreDisease responses of eight wheat cultivars , Saber Beg. , Abu-Ghraib 3, Mexipak , Tamoz 2,Tamoz 3 , IPA 95 ,IPA 99 and Tahadi which were grown in four different sowing date , 25 th October , 19th September , 14th December and 8 January , to leaf rust disease caused by Puccinia recondita were investigated under natural infection conditions at the experimental farm , College of Agriculture , Abu-Ghraib, during the growing season of 1997-1998.Results of this study revealed that IPA 95, IPA 99 and Tahadi showed moderate resistant reaction, while Tamuz 3 was moderateley susceptable . Abu-Ghraib , Saber Beg, Tamuz 2 and Mexipak showed susceptible yeaction to the causal agent . The first sowing date was not suitable for disease progress in compars
... Show MoreThe Effect of Chicken Eggshell Extract on Microhardness of Artificially Induced Dental Erosion in Permanent Teeth (In Vitro Study), Shatha A Abbas*, Alhan A Qasim