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.
While many educators are highly focused on state test, it is important to consider that
over the course of a year, instructors can build in many opportunities to assess how learners
are learning. Therefore, assessment techniques are considered a good method to get benefit
for both instructors and learners in the process of teaching and learning. The sample consists
of 27 learners who participated in TOEFL training course in the Development and Continuous
Education Centre. Validity and reliability were verified.
To fulfill the aims and verify the hypothesis which reads as follows” It is hypothesized
that the TOEFL learners' scores will not be increased after TOEFL course training.” T-test
for two dependent samp
The speed of skills has become linked to modern methods of individual and group play, and each of them has begun to serve the other tactically. Through the follow-up of the researchers, they noticed that there is a significant weakness in the speed of performance and slowness in mental preparation, which plays a major role in understanding mental readiness, which is linked to the speed of making decisions during the game, as well as the weakness of the physical speed of the female players, which in turn has an impact on the skill performance of the players of the Iraqi clubs, which are the main supporter of the national team. The study aimed to identify the effect of interactive speed training on the performance of some skills among
... Show MoreIn this work an approach has been developed to investigate the influence of surface roughness on thermohydrodynamic performance in aligned and misaligned journal bearings by considering an average flow model and deriving the shear flow factor for various roughness configurations, similar to the pressure flow factor. An average Reynolds equation for rough surfaces is defined in term of pressure and shear flow factors, which can be obtained by numerical flow simulation, though the use of measured or numerically generated rough surfaces. Reynolds, heat conduction and energy equations are solved simultaneously by using a suitable numerical technique (Finite Difference Method) to obtain the pressure and temperature di
... Show MoreIn the current research, we investigated the absorption spectrum for R590 and C480 dyes in ethanol solvent for different dye solution concentrations of 10-4, 10-5 and 10-6M. These dyes have been prepared and studied before and after gamma irradiation (first, second ionization) using cesium-137 source with absorbed doses of 18.36 Gy (time exposure of 10 days) and 73.44 Gy (with time exposure of 40 days). We noticed that the absorption intensity was decreased with decreasing concentration, before gamma irradiation while the absorption spectrum peak shifted towards the short wavelength (blue shift). It was also found that the intensity of absorption spectrum increased and shifted the absorption spectrum peak towards the long wavelength (red
... Show MoreElectrospun nanofiber membranes are employed in a variety of applications due to its unique features. the nanofibers' characterizations are effected by the polymer solution. The used solvent for dissolving the polymer powder is critical in preparing the precursor solution. In this paper, the Polyacrylonitrile (PAN)-based nanofibers were prepared in a concentration of 10 wt.% using various solvents (NMP, DMF, and DMSO). The surface morphology, porosity, and the mechanical strength of the three prepared 10 wt.% PAN-based nanofibers membranes (PAN/NMP, PAN/DMF, and PAN/DMSO) were characterized using the Scanning Electron Microscopy (SEM), Dry-wet Weights method, and Dynamic Mechanical Analyzer (DMA). Using DMF as a solvent resulted in a lon
... Show MoreOver the last few decades, many instructors have been trying all kinds of teaching methods, but without benefit. Nevertheless, in the 1986, a new technique is appeared which called K-W-L technique, it is specified for reading comprehension passages because reading skill is not easy matter for students for specific purposes (ESP).therefore, the K-W-L technique is a good one for thinking and experiences. To fulfill the aims and verify the hypothesis which reads as follows" it is hypothesized that there are no significant differences between the achievements of students who are taught according to K-W-L technique and those who are taught according to the traditional method
... Show MoreA new pavement technology has been developed in Highway engineering: asphalt pavement production is less susceptible to oxidation and the consequent damages. The warm mix asphalt (WMA) is produced at a temperature of about (10-40) oC lower than the hot asphalt paving. This is done using one of the methods of producing a WMA. Although WMA's performance is rather good, according to previous studies, as it is less susceptible to oxidation, it is possible to modify some of its properties using different materials, including polymers. Waste tires of vehicles are one of the types of polymers because of their flexible properties. The production of HMA, WMA, and WMA modified with proportions of (1, 1.5, and 2%) of rub
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