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 photooxidative degradation process of plastics caused by ultraviolet irradiation leads to bond breaking, crosslinking, the elimination of volatiles, formation of free radicals, and decreases in weight and molecular weight. Photodegradation deteriorates both the mechanical and physical properties of plastics and affects their predicted life use, in particular for applications in harsh environments. Plastics have many benefits, while on the other hand, they have numerous disadvantages, such as photodegradation and photooxidation in harsh environments and the release of toxic substances due to the leaching of some components, which have a negative effect on living organisms. Therefore, attention is paid to the design and use of saf
... Show MoreThe excellent specifications of electrodes coated with lead dioxide material make it of great importance in the industry. So it was suggested this study, which includes electrodeposition of lead dioxide on graphite substrate, knowing that the electrodeposition of lead dioxide on graphite studied earlier in different ways.
In this work the deposition process for lead dioxide conducted using electrolytic solution containing lead nitrate concentration 0.72 M with the addition of some other material to the solution, such as copper nitrate, nickel nitrate, sodium fluoride and cetyl trimethyl ammonium bromide, but only in very small concentrations. As for the operating conditions, the effect of change potential and temperature as well
... Show MoreValues are penetrating or interfering in the lives of individuals and groups and are connected to them in the sense of life itself, because they are closely linked to the motives of behavior, hopes and goals, and can be said that values are everything. The concept of values is one of the concepts that have received the attention of researchers from different disciplines. This has resulted in a kind of confusion and variation in use from one specialization to the other, and uses multiple uses within one specialization. Therefore, there is no uniform definition of values because they relate to individuals. Individuals differ in many things, such as perception,
... Show MoreThe study of Mars's ionosphere was made by investigating the measurements of the electron density (Ne) depending of the variation of the solar activities through different local time, different seasons, and different altitudes. The datasets has been taken from MARSIS on board the Mars Express spacecraft, the investigation for the solar indices and the electron density (Ne) have been made for two period of time depending on the strength of the geomagnetic storms, the first one was taken when the geomagnetic storms was low as in years (1998 & 2005), the data was chosen for three seasons of these years, Winter (December), Summer (June) and Spring (April). The second period was taken for the years (2001 & 2002) when the geomagnetic s
... Show MoreMatrix acidizing is a good stimulation process in which acid is introduced into the reservoir near the wellbore area via the wellbore or coil tubing. In the oil industry, formation damage is a prevalent problem. Bypassing wellbore damage by producing wormholes in carbonate reservoirs is the main purpose of acidizing the matrix of the formation. When doing lab tests, scientists are looking for a wormhole-inducing injection rate that can be used in the field. Meantime the ongoing works on the Ahdeb oil field's Mishrif reservoir, several reports have documented the difficulties encountered during stimulation operations, including high injection pressures that make it difficult to inject acid into the reservoir formation; and only a few
... Show MoreThe artistic process operates whether in general in all arts or specifically in one type of arts or one of the genres of arts types on the preoccupations of the pressing artistic references as the founder of the artistic work in the material formulations on the one hand and on the other hand as a translator to understand the artistic achievement in general and plastic art in particular and for the importance The researcher chose the title of her research tagged (the preoccupations of the pressing reference and its impact on the formations of postmodern arts).
The first chapter of the methodological framework deals with the problem of research, importance, objective, limits, and then terminology and its definition, and then the secon
The study of Mars's ionosphere was made by investigating the measurements of the electron density (Ne) depending of the variation of the solar activities through different local time, different seasons, and different altitudes. The datasets has been taken from MARSIS on board the Mars Express spacecraft, the investigation for the solar indices and the electron density (Ne) have been made for two period of time depending on the strength of the geomagnetic storms, the first one was taken when the geomagnetic storms was low as in years (1998 & 2005), the data was chosen for three seasons of these years, Winter (December), Summer (June) and Spring (April). The second period was taken for the years (2001 & 2002) when the geomagnetic s
... Show MoreDue to the increasing interest in the quality of auditing by writers, researchers and regulators of the auditing profession. The matter necessitated a statement of the extent to which the auditor practices professional skepticism, because of its significant impact in discovering errors and material misrepresentations contained in the financial statements in order to give the financial community confidence in them and the success of the audit process. The research aims to clarify the concept and importance of the practice of professional skepticism and its effect on the quality of the auditor's performance in Iraq. To achieve the research objectives, the two re
... Show MoreAim: This abstract aims to highlight the critical nature of climate change as a pressing challenge facing humanity in the 21st century. It underscores the severe consequences it poses to essential facets of human existence, including water and energy resources, agricultural production, and the broader environmental systems. Method: The abstract primarily utilizes a descriptive approach to emphasize the impact of climate change on the Middle East, particularly the Arab region. It relies on a review of existing knowledge and data related to climate change and its effects on ecosystems and drought patterns. Results: The abstract outlines the direct and indirect repercussions of climate change on human life and the environment. It draws atten
... Show MoreCoaxial (wire-cylinder) electrodes arrangements are widely used for electrostatic deposition of dust particles in flue gases, when a high voltage is applied to electrodes immersed in air and provide a strongly non-uniform electric field. The efficiency of electrostatic filters mainly depends on the value of the applied voltage and the distribution of the electric field. In this work, a two-dimensional computer simulation was constructed to study the effect of different applied voltages (20, 22, 25, 26, 28, 30 kV) on the inner electrode and their effect on the efficiency of the electrostatic precipitator. Finite Element Method (FEM) and COMSOL Multiphysics software were used to simulate the cross section of a wire cylinder. The results sh
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