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.
Годы, принадлежащие концу XIX – началу XX столетия, вошли в русскую литературу под красивым названием Серебряный век. В это время в стране появился целый ряд выдающихся поэтов, имена которых навсегда останутся в русской и мировой литературе. Это Ахматова, Гумилев, Блок, Маяковский и многие другие. Все эти люди творили в нелегкое для России время. Началом Серебряного века условно считают 189
... Show MoreAbstract The study aims to clarify the value of auditing economic units and how it can be measured, which is one of the most important challenges to matching the Value Relevance of Accounting Information. The problem of the study was identified with questions that revolve around the extent to which it is possible to measure the value of auditing in Iraqi economic units and the extent to which the value of auditing affects the adequacy of accounting information. Through reviewing the studies discussing this topic, it was found that auditing can provide value through the performance of the auditor and adding value to the economic unit subject to audit. The study recommended the need to study the situational factors of auditing, whether exter
... Show MoreThe research aims to identify the effect of the PQ5R strategy on the achievement of chemistry among fifth-grade science students in government secondary and preparatory schools. Al-Zumar Girls High School was chosen as its students as the research sample affiliated with the Diyala Education Directorate, Diyala Education Department, for the academic year (2023-2024). and Two divisions were chosen from among divisions. The fifth scientific grade was chosen randomly, one of them was the experimental group taught according to the PQ5R strategy, and the other was the control group taught according to the usual method. The equality of the two research groups was verified with a set of variables, which were (chronological age in months, previous a
... Show Morethe shear strength parameters of the treated and untreated gypsum soil under the effect of four soaking and drying cycles has studied in this paper, moreover examined the effect of wetting and drying cycles on the collapse potential of the soil and comparing between the behavior of the treated and untreated gypsum soil under the effect of the two conditions. Gypsum soil sample brought from Sawa lake in Al Muthana governorate with the content of gypsum 65.5%, the polyurethane polymer (PP) was used with different percentages 3, 6, and 10% to enhance the mechanical properties of gypsum soil, model was prepared to achieve four soaking and drying cycle to the samples before testing, this model consists of an Aluminum plate base with dimensions 7
... Show MoreThe purpose of this study is to investigate the effect of credit risk indicators on the Arab Gulf countries' banks Profitability over the period of 2015 to 2017. The banking credit risk was calculated using non-performing loans ratio affecting banks profitability indicators like net income and by using fixed effect and random effect model analyses, the study found that increasing in non-performing loans ratio will decrease the net income in gulf banks, the study also found that personal loans represent the largest share of loans granted in gulf banks. Also, the study recommends the importance of developing the capabilities of credit departments in commercial banks in dealing with bad loans, and studying the financial statem
... Show MoreThis research deals with the effect of constructive conflict of the organizational identification .These relatively recent subjects have relative importance in the field of administration and they have strong effect in the success of organizations .The objective of this research is to detect the level of the constructive conflict and the organizational identification in the center of The Ministry of Planning. So, two major hypotheses were formulated The first are searched the correlation between the constructive conflict and the organizational identification and it emerged with four sub-hypotheses searched the correlation among every dimension of the constructive conflict with the organizational identification .The second major h
... Show MoreSloped solar chimney system is a solar chimney power plant with a sloped collector. Practically, the sloped collector can function as a chimney, then the chimney height can be reduced and the construction cost would be reduced.The continuity, Naver-stockes, energy and radiation transfer equations have been solved and carried out by Fluent software. The governing equations are solved for incompressible, 3-D, steady, turbulent standard model with Boussiuesq approximation to develop for the sloped solar chimney system in this study and evaluate the performance of solar chimney power plant in Baghdad city of Iraq numerically by Fluent (14) software with orking conditions such as solar radiation intensity (30
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