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.
Background: Behçet’s disease (BD) is a disorder of systemic inflammatory condition. Its important features are represented by recurrent oral, genital ulcerations and eye lesions. Aims. The purpose of the current study was to evaluate and compare cytological changes using morphometric analysis of the exfoliated buccal mucosal cells in Behçet’s disease patients and healthy controls, and to evaluate the clinical characteristics of Behçet’s disease. Methods. Twenty five Behçet’s disease patients have been compared to 25 healthy volunteers as a control group. Papanicolaou stain was used for staining the smears taken from buccal epithelial cells to be analyzed cytomorphometrically. The image analysis software has been used to
... Show MoreBackground BK polyomavirus is one of the common post-transplant viral infections, affecting ∼15% of renal transplantation recipients (RTR), leading to graft loss in more than half of cases. Objectives Study the rate of detection of BK virus (BKV) in RTRs in Pap-stained urine cytology specimens. Methods A single center study, urine samples were collected from 99 RTR patients, with 15 Living Donors (LD) and 15 patients with chronic kidney disease (CKD) were taken as controls. And urine cytology smears were Pap stained for detection of decoy cells (DCs). Results Out of the 99 RTRs, 27 (27.3%) patients were decoy positive, 8 out of these 27 patients had uncommon DCs, and 5 out of these 27 cytology positive patients (18.5%) had biopsy proven B
... Show MoreSolar energy has significant advantages compared to conventional sources such as coal and natural gas, including no emissions, no need for fuel, and the potential for installation in a wide range of locations with access to sunlight. In this investigation, heterocyclic derivatives were synthesized from several porphyrin derivatives (4,4',4",4"'-(porphyrin-5,10,15,20-tetrayl) tetra benzoic acid) compound (3), obtained by reaction Pyrrole with 4-formyl benzoic acid. Subsequently, porphyrin derivative-component amides 5a, 5b, and 5c were produced by reacting compound (3) with amine derivatives at a 1:4 molar ratio. These derivatives exhibited varying sensitivities for utilization in solar cells, with compound 5a displaying the highest power
... Show MoreABSTRACT:
Interest rates are one of the important aspects that affect the banking business directly, which is characterized by unstable dynamic dynamics, which must be viewed on a daily and continuous basis through the macroeconomic view, which directly affects the bank’s income realized from loans as interest received or interest paid on its deposits as an expense. Hence the earnings per share. The relationship between interest rates and between net income and earnings per share was measured and a correlation was found between them, and then the effect between them was measured using regression equations and they were applied and th
... Show MoreGypseous soil covers approximately 30% of Iraqi lands and is widely used in geotechnical and construction engineering as it is. The demand for residential complexes has increased, so one of the significant challenges in studying gypsum soil due to its unique behavior is understanding its interaction with foundations, such as strip and square footing. This is because there is a lack of experiments that provide total displacement diagrams or failure envelopes, which are well-considered for non-problematic soil. The aim is to address a comprehensive understanding of the micromechanical properties of dry, saturated, and treated gypseous sandy soils and to analyze the interaction of strip base with this type of soil using particle image
... Show MoreBackground: Asthma is a common chronic disease in children in which the body’s airways swell, preventing the lungs from filling with air, there are many different inflammatory cells involved in asthma which can synthesize and release cytokines which are recognized to be important in chronic inflammation and play a critical role in the inflammatory response. Objectives: to assess the local effect of ICS on oral tissue by measuring Interlukine-12 level and Candida albicans colony in saliva among12 year's old asthmatic children who were collected from AL- Zahra Center Advisory for Allergy and Asthma, and compares them with non-asthmatic children of the same age and gender.Type of the study: Cross –sectional study.Methods: The total samp
... Show Moret-Self-Compacting Concrete (SCC) reduces environmental noise and has more workability. This research presents an investigation of the behavior of SCC under mechanical loading (impact loading). Two types of cement have been used to produce SCC mixtures, Ordinary Portland Cement (OPC) and Portland Limestone Cement (PLC), which reduces the emission of carbon dioxide during the manufacturing process. The mixes were reinforced with Carbon Fiber Reinforced Polymer (CFRP) which is usually used to improve the seismic performance of masonry walls, to replace lost steel reinforcements, or to increase column strength and ductility. Workability tests were carried out for fresh SCC. Prepared concrete slabs of 500×500×50mm were tested for lo
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