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.
This study was designed to evaluate the effect of aqueous extract of Arabidopsis thaliana seeds on reducing glucose level for white albino mice. Twenty adults mice were used, divided randomly into four groups (five mice per each group). The first group (normal mice) was administrated with 0.1 ml of distilled water as a control, the second group (normal mice) was administrated with 0.1 ml of the plant extract, whereas the third and fourth groups (diabetic mice) were administrated with single dose of alloxan (150 mg/kg of the body weight) to induce diabetes, and the fourth group was administrated with 0.1 ml of the plant extract for 10 days, then blood glucose level was measured for all of the experimental animals (diabetic and no
... Show MoreThis paper is focused on studying the effect of cutting parameters (spindle speed, feed and depth of cut) on the response (temperature and tool life) during turning process. The inserts used in this study are carbide inserts coated with TiAlN (Titanum, Aluminium and Nitride) for machining a shaft of stainless steel 316L. Finite difference method was used to find the temperature distribution. The experimental results were done using infrared camera while the simulation process was performed using Matlab software package. The results showed that the maximum difference between the experimental and simulation results was equal to 19.3 , so, a good agreement between the experimental and simulation results was achieved. Tool life w
... Show MoreNowadays, university education stands in front of both students who feel they are weak and teachers who are addicted to using traditional and dependent teaching. This has led to have negative repercussions on the learner from different aspects, including the mental aspect and the academic achievement process. Therefore, the present research is concerned with finding a new teaching method that adopts the motivation by the fear of failure technique. Thus, the study aims to examine the effect of adopting this method on students’ academic achievement. To achieve this aim, an experimental method was used, and an achievement test was built for the curriculum material of level two students. The pretest test was applied on 17 male and female s
... Show MoreBackground: One of the most predominant periodontal diseases is the plaque induced gingivitis. For the past 20 years, super-oxidized solutions have be..
The problem of present study is determined by answering the following questions:
1) What is the effect of using the oral open- ended questions on Students' achievement in the third-stage of Arabic department in the college of Education? 2) What is the effect of the oral open-ended questions on developing the creative thinking of students in
... Show MoreThis study aimed to isolate and identifye the growth of microorganisms and
their effect on pickled cucumber and cabbage, the study also investigated the effect of
garlic (in the form of segments, chopped or crushed) on the mentioned pickled –food
features . Furthermore, a sense based comparison is made between vinegar-preserved
samples and vinegar-garlic preserved ones.
The following results have been obtained:
1- The isolation of staph. aureus alone from the samples and the study of its physical
and biochemical features.
2- The fresh garlic (segments, chopped and crushed) with concentration of 5%, 7.5%,
and 10% showed a damaging percentage of 100% to bacterial growth of staph. Aureus
after 24 hours of inc