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Publication Date

Tue Aug 15 2017

Journal Name

Journal Of Immunology

Volume

199

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The Effect of Inhibitory Signals on the Priming of Drug Hapten–Specific T Cells That Express Distinct Vβ Receptors

Andrew

Lee

Maike

Monday

Zaid

Ana

Philipp R.

Stefan F.

Munir

B. Kevin

Dean J.

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Abstract<p>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.</p>

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Publication Date

Fri Jan 13 2023

Journal Name

Journal Of The Faculty Of Medicine Baghdad

Detection of Chronic Obstructive Pulmonary Disease among Smokers Aged ≥40 years Attending Primary Health Care Centers in Baghdad-AL-Karkh and AL-Resafa: الكشف عن الالكشف عن مرض الانسداد الرئوي المزمن بين المدخنين الذين تزيد أعمارهم عن 40 عامًا يراجعون مراكز الرعاية الصحية الأولية في بغداد - الكرخ و الرصافة

Isra A.

Nada Abdul Wahhab

Faris

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Background: Chronic obstructive pulmonary disease causes permanent morbidity, premature mortality and great burden to the healthcare system. Smoking is it's most common risk factor and Spirometry is for diagnosing COPD and monitoring its progression.

Objectives: Early detection of chronic obstructive pulmonary disease in symptomatic smokers’ ≥ 40years by spirometry.

Methods: A cross sectional study on all symptomatic smokers aged ≥ 40 years attending ten PHCCs in Baghdad Alkarkh and Alrisafa. Those whose FEV1/FVC was <70% on spirometry; after giving bronchodilator, were considered COPD +ve.

Results: Overall, airway obstruction was seen in

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