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 medicinal plants (Astragalus species) have been used traditionally as anti-inflammatory, antioxidant, and Anti-diabetics. The current research investigates the phytochemistry and some biological activity of methanol extract of different parts of Astragalus bruguieri Bioss., a wild medicinal plant grows on Safeen mountain, Erbil, Iraq. The methanol extracts of A. bruguieri were analyzed for total phenolic, flavonoid, and saponin contents. In-vitro antioxidant activity was analyzed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays. Furthermore, the plant extracts were examined for in-vitro enzyme inhibitory activity and in-v
... Show MoreWe report herein an innovative approach to prostate tumor therapy using tumor specific radioactive gold nanoparticles (198Au) functionalized with Mangiferin (MGF). Production and full characterization of MGF-198AuNPs are described. In vivo therapeutic efficacy of MGF-198AuNPs, through intratumoral delivery, in SCID mice bearing prostate tumor xenografts are described. Singular doses of the nano-radiopharmaceutical (MGF-198AuNPs) resulted in over 85% reduction of tumor volume as compared to untreated control groups. The excellent anti-tumor efficacy of MGF-198AuNPs are attributed to the retention of over 90% of the injected dose within tumors for long periods of time. The retention of MGF-198AuNPs is also rationalized in terms of the higher
... Show MoreIn this paper we prove the boundedness of the solutions and their derivatives of the second order ordinary differential equation x ?+f(x) x ?+g(x)=u(t), under certain conditions on f,g and u. Our results are generalization of those given in [1].
The effect of insecticide lamda cyhalothrin on Allium cepa L.root meristem were studied cytogenetically .Using three concentrations of the insecticide 5%, 7.5%, 10% at 6,12,24hours treatments . The insecticide significantly reduced the mitotic index at all concentrations. Moreover showed its ability to induced C – metaphase in 10% .The effects were also caused chromosome aberration like stickness in anaphase, telophase, binucleated cells, Micronuclei formation. These alternations indicating that this insecticide was effective in producing disturbance of spindle fibers.
THE EFFECT OF SPREACL of KNOWLEDGE ON ETHICS
Thin film solar cells are preferable to the researchers and in applications due to the minimum material usage and to the rising of their efficiencies. In particular, thin film solar cells, which are designed based one transition metal chalcogenide materials, paly an essential role in solar energy conversion market. In this paper, transition metals with chalcogenide Nickel selenide termed as (NiSe2/Si) are synthesized. To this end, polycrystalline NiSe2 thin films are deposited through the use of vacuum evaporation technique under vacuum of 2.1x10-5 mbar, which are supplied to different annealing temperatures. The results show that under an annealed temperature of 525 K,
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