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.
چکیدهی بحث
به نظر میآید که عالم هستی ، بر مسألهی « حرکت» استوار دارد ، و روح ، همیشه دنبال دگرگونی و تکامل و برتری میگردد. حرکت ، همهی چیزها در عالم إمکان را در بر میگیرد. حرکت در بنیادهای فکر مولانا جای مهمی دارد .اشعار مولانا مقدار زیادی از پویایی و حرکت برخوردارست، و از آنجایی که فعل ، عنصر تکانبخش جمله ، و کانون دلالت است ، ترجیح دادیم - علاوه بر دیگر عنا
... Show MoreThe Co (II), Ni (II) ,Cu(II), Zn(II) ,Cd(II) and Hg(II) complexes of mixed of amino acid (L-Alanine ) and Trimethoprim antibiotic were synthesized. The complexes were characterized using melting point, conductivity measurement and determination the percentage of the metal in the complexes by flame (AAS). Magnetic susceptibility, Spectroscopic Method [FT-IR and UV-Vis]. The general formula have been given for the prepared mixed ligand complexes [M(Ala)2(TMP)(H2O)] where L- alanine (abbreviated as (Ala ) = (C5H9NO2) deprotonated primary ligand, L- Alanine ion .= (C5H8NO2-) Trimethoprim (abbreviated as (TMP ) = C10H11N3O3S M(II) = Co (II),Ni(II) ,Cu(II), Zn(II) ,Cd(II) and Hg(II). The results showed that the deprotonated L- Alanine b
... Show MoreThe nuclear charge density distributions, form factors and
corresponding proton, charge, neutron, and matter root mean square
radii for stable 4He, 12C, and 16O nuclei have been calculated using
single-particle radial wave functions of Woods-Saxon potential and
harmonic-oscillator potential for comparison. The calculations for the
ground charge density distributions using the Woods-Saxon potential
show good agreement with experimental data for 4He nucleus while
the results for 12C and 16O nuclei are better in harmonic-oscillator
potential. The calculated elastic charge form factors in Woods-Saxon
potential are better than the results of harmonic-oscillator potential.
Finally, the calculated root mean square
The formation of Co(II), Ni(II), Cu(II), Zn(II), and Cd(II)-complexes (C1-C5) respectively was studied with new Schiff base ligand [benzyl(2-hydroxy-1-naphthalidene) hydrazine carbodithioate derived from reaction of 2-hydroxy-1-naphthaldehyde and benzyl hydrazine carbodithioate. The suggested structures of the ligand and its complexes have been determined by using C.H.N.S analyzer, thermal analysis, FT-IR, U.V-Visible, 1HNMR, 13CNMR , conductivity measurement , magnetic susceptibility and atomic absorption. According to these studies, the ligand coordinates as a tridentate with metal ions through nitrogen atom of azomethane , oxygen atom of hydroxyl, and sulfur atom of thione
... Show MoreThe ligand 4-(2-aminmo-5-nitro-phenylazo)-1,5-dimethyl-2-phenyl-1,2-dihydro-pyrazol-3-one derived from 4-aminoantipyrine and 4-nitroaniline was synthesized. The synthesized ligand was characterized by 1HNMR, FT-IR, UV-Vis spectra and (C.H.N) analysis. Complexes of (YIII and LaIII ) with the ligand were prepared in aqueous ethanol with a 1:2 M:L ratio and at optimum pH. The prepared complexes were characterized by using flame atomic absorption, FT-IR, UV-Vis spectra,(C.H.N) analysis and conductivity measurement. The stoichiometry of complexes was studied by the mole ratio and job methods. A concentration range (1×10-4 - 3×10-4 M) obeyed Beer's law, the complex solutions show high values of molar absorption. On the basis of physicochemical
... Show MoreWe report here an innovative feature of green nanotechnology-focused work showing that mangiferin—a glucose functionalized xanthonoid, found in abundance in mango peels—serves dual roles of chemical reduction and in situ encapsulation, to produce gold nanoparticles with optimum in vivo stability and tumor specific characteristics. The interaction of mangiferin with a Au-198 gold precursor affords MGF-198AuNPs as the beta emissions of Au-198 provide unique advantages for tumor therapy while gamma rays are used for the quantitative estimation of gold within the tumors and various organs. The laminin receptor specificity of mangiferin affords specific accumulation of therapeutic payloads of this new therapeutic agent within prostate tumors
... Show MoreBackground: In young adults, multiple sclerosis is a prevalent chronic inflammatory demyelinating condition. It is characterized by white matter affection, but many individuals also have significant gray matter involvement. A double-inversion recovery pulse (DIR) pattern was recently proposed to improve the visibility of multiple sclerosis lesions. Objective: To find out how well a DIR sequence, FLAIR, and T2-weighted pulse sequences can find MS lesions in the supratentorial and infratentorial regions. Methods: A total of 37 patients with established diagnoses of multiple sclerosis were included in this cross-sectional study. Brain MRI was done using double inversion recovery, T2, and FLAIR sequences. The number of lesions was count
... Show MoreThe nuclear charge density distributions, form factors andcorresponding proton, charge, neutron, and matter root mean squareradii for stable 4He, 12C, and 16O nuclei have been calculated usingsingle-particle radial wave functions of Woods-Saxon potential andharmonic-oscillator potential for comparison. The calculations for theground charge density distributions using the Woods-Saxon potentialshow good agreement with experimental data for 4He nucleus whilethe results for 12C and 16O nuclei are better in harmonic-oscillatorpotential. The calculated elastic charge form factors in Woods-Saxonpotential are better than the results of harmonic-oscillator potential.Finally, the calculated root mean square radii usingWoods-Saxonpotentials ho
... Show MoreThe new 4-[(7-chloro-2,1,3-benzoxadiazole)azo]-4,5-diphenyl imidazole (L) have been synthesized and characterized by micro elemental and thermal analyses as well as 1H.NMR, FT-IR, and UV-Vis spectroscopic techniques. (L) acts as a ligand coordinating with some metal ionsV(IV), Fe(III), Co(II), Ni(II), Cu(II), and Zn(II). Structures of the new compounds were characterized by elemental and thermal analyses as well as FT-IR and UV-Vis Spectra. The magnetic properties and electrical conductivities of metal complexes were also determined. Study of the nature of the complexes formed in ethanol following the mole ratio method.. The work also include a theoretical treatment of the formed complexes in the gas phase, this was done using the (hyperch
... Show More