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.
The last four decades have witnessed a number of rapid and successive international changes in terms of future impacts and orientations. International economy has transformed into a competitive small village due to the information technology revolution and the liberation processes and the economic openness that the market witnesses, there became one market and the activists in this international market are not governments only but rather international organizations and huge multinational corporations where each spares no effort to take every opportunity and face challenges within the frame of removing all impediments and release transactions under the auspices of these global developments, the idea of creating Islamic
... Show MoreThe aim of this study was intended to study the effect of rifampicin in the level of thyroid's gland hormones (T4 ØŒT3) and thyroid -stimulating hormone (TSH) in rabbits. Eight male rabbits were used through out this study, their weights were measured before the starting of the experiment. Animals were divided into two groups (each group contains 4 rabbits), the first group was administrated daily with 15 mg/Kg physiological normal saline for 35 days and used as a control group, while the second group was administrated with 15 mg /Kg daily for 35 day of rifampicin capsule 300 mg. At the end of the experiment, all of animal groups were
... Show MoreThe Journal of Studies and Researches of Sport Education (JSRSE)
This research includes a study of the effect of four temperatures (25, 30, 35, 40m◦) with relative humidity 65% on some biological aspects of the Bean beetle Acanthoselides obtectus on the Bean seeds under laboratory conditions. The results showed that the effect of different temperatures is clear on biological of Bean beetle. Differed period necessary for the growth and development of each stage of the insect in different temperatures . The results of statically analysis showed a significant difference in the life cycle when all temperatures except the period between temperature 35 and 40m◦ , respectively. Where the average of those period, 60.75, 35.5, 20.34 and 19.27 days and also different temperatures significant effects is clea
... Show MoreThe effects of land use/cover change are recognized as one of the challenges facing humans in the twenty-first century. In contrast to less developed regions, its characteristics are characterized by a variety of climatic conditions. The changes result in “Urban Heat Island”, in which the temperature in cities is higher than the temperature in the rest of the country. By monitoring the city of Baghdad for a short period, Baghdad's urbanization progressed quickly, which negatively affected the region’s climate through the decreasing of agricultural lands surrounding the area. Understanding the extent of effects on the environment is critical for long-term development. Climate change and environmental cleanup include making the right
... Show MoreThe present study aims at knowing the effect of instrumental enrichment in the acquisition of geographical concepts for first grade student in intermediate school. The study is restricted in the students of first grade student in intermediate school\ The EducationalDirectorate of Rusafa for academic (2013/2014),for the purpose of achieving the objective, the following hypotheses:
There is no statistical significant different at the level of (0.5) between the scores of the experimental group who study geography according to the instrumental enrichment and the scores of the control group who learned geographical according to the traditional methods.
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