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 Intrahepatic cholestasis is clinical syndrome which cause either by defect in synthesis or bile acid flow, the pathophysiology of cholestasis is complicated by a number of variables, including oxidative stress, inflammatory response, and dysregulation of bile acid transporter . Rats, mice, and guinea pigs were utilized as experimental animals, and ANIT was administered to them in order to create a model that closely resembled intrahepatic cholestasis in human. This study examined the protective effects of papaverine, a non-narcotic opium alkaloid derived from papaver somniferum and discovered as an FXR agonist, on cholestasis in rats induced by alpha-naphthylisothiocyanate (ANIT). Rats utilized in this study divid
... Show MoreThin films of Mn2O3 doped with Cu have been fabricated using the simplest and cheapest chemical spray pyrolysis technique onto a glass substrate heated up to 250 oC. Transmittance and absorptance spectra were studied in the wavelength range (300 -1100) nm. The average transmittance at low energy was about 60% and decrease with Cu doping, Optical constants like refractive index, extinction coefficient and dielectric constants (εr), (εi) are calculated and correlated with doping process.
The investigation of the effect of tempering on thermal analysis of
Al-Ti-Si alloy and its composites with MgO and SiC particles was
performed. Thermal analysis was performed before and after
tempering by DSC scan. Optical microscopy was used to identify the
phases and precipitations that may be formed in base alloy and
composites. X-ray diffraction test indicated that the Al3Ti is the main
phase in Al-Ti-Si alloy in addition to form Al5Ti7Si12 phase. Some
chemical reactions can be occurred between reinforcements and
matrix such as MgO.Al2O3 in Al-Ti/MgO, and Al4C3 and Al(OH)3 in
Al-Ti/SiC composite. X-ray florescence technique is used to
investigate the chemical composition of the fabricated specimens.
H
This study was conducted to explore the effects of using ionized water on the productive and physiological performance of Japanese quails (Coturnix japonica). Our study was conducted at a private farm from 20th April, 2016 to 13th July, 2016 (84 d). One hundred 42-day-old Japanese quail chicks were used, divided randomly into 5 groups with 4 replicates. Treatments consisted in a control group (T1 - normal water:), alkaline (T2 - pH 8 and T3 - pH 9), and acidic water (T4 - pH 6 and T5 - pH 5). All birds were fed a balanced diet of energy and protein. The egg production ratio, egg weight, cumulative number of eggs, egg mass, feed conversion ratio, productivity per hen per week, and effects on plasma lipids, uric acid, glucose, calcium, and ph
... Show MoreNanofluid treatment of oil reservoirs is being developed to enhance oil recovery and increase residual trapping capacities of CO2 at the reservoir scale. Recent studies have demonstrated good potential for silica nanoparticles for enhanced oil recovery (EOR) at ambient conditions. Nanofluid composition and exposure time have shown significant effects on the efficiency of EOR. However, there is a serious lack of information regarding the influence of temperature on nanofluid performance; thus the effects of temperature, exposure time and particle size on wettability alteration of oil-wet calcite surface were comprehensively investigated; moreover, the stability of the nanofluids was examined. We found that nanofluid treatment is more efficie
... Show MoreThis paper is devoted to investigate the effect of internal curing technique on the properties of self-compacting concrete. In this study, self-compacting concrete is produced by using limestone powder as partial replacement by weight of cement with percentage of (5%), sand is partially replaced by volume with saturated fine lightweight aggregate which is thermostone aggregate as internal curing material in three percentages of (5%, 10%, 15%) for self-compacting concrete, and the use of two external curing conditions which are water and air. The experimental work was divided into three parts: in the first part, the workability tests of fresh self-compacting concrete were conducted. The second part included conducting compressive str
... Show MoreIn this research the effect of cooling rate and mold type on mechanical properties of the eutectic
and hypoeutectic (Al-Si) alloys has been studied. The alloys used in this research work were (Al- 12.6%Si
alloy) and (Al- 7%Si alloy).The two alloys have been melted and poured in two types of molds with
different cooling rates. One of them was a sand mold and the other was metal mold. Mechanical tests
(hardness, tensile test and impact test) were carried out on the specimens. Also the metallographic
examination was performed.
It has been found that the values of hardness for the alloys(Al-12.6%Si and Al-7%Si) which poured in
metal mold is greater than the values of hardness for the same alloy when it poured in a heated
This study was carried out to estimate the effect of shaliness on water saturation from TN field of Niger Delta. The conventional Archie and the Shaly-sand water saturation models was used in the evaluation of wells. Two sand bodies (Sand 01 and 02) were mapped with thicknesses range from 76.8ft to 119.3ft across the three wells for Sand 01 and 187.5 to 339.9ft across wells TN_1 and TN_4 for Sand 02. The cross plot of the effective porosity (φe) versus volume of shale (Vsh) show a decrease in the effective porosity with an increase in shale volume. This reveals a laminated shale pattern across the reservoir sands. The estimations from the conventional method and the Shaly-sand models of Simandoux and Indonesia show a clear disparity due
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