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首页> 外文期刊>Cellular immunology >HLA-DR*0401 expression in the NOD mice prevents the development of autoimmune diabetes by multiple alterations in the T-cell compartment
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HLA-DR*0401 expression in the NOD mice prevents the development of autoimmune diabetes by multiple alterations in the T-cell compartment

机译:HLA-DR * 0401在NOD小鼠中的表达可通过T细胞区室的多种改变阻止自身免疫性糖尿病的发展

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摘要

Several human HLA alleles have been found associated with type 1 diabetes (T1D), but their precise role is not clearly defined. Herein, we report that a human MHC class II (HLA-DR*0401) allele transgene that has been expressed into NOD (H-2(g7)I-E-null) mice prone to T1D rendered the mice resistant to the disease. T1D resistance occurred in the context of multi-point T-cell alterations such as: (i) skewed CD4/CD8 T-cell ratio, (ii) decreased size of CD4(+)CD44(high) T memory pool, (iii) aberrant TCR V beta repertoire, (iv) increased neonatal number of Foxp3(+) and TR-1(+) regulatory cells, and (v) reduced IFN-gamma inflammatory response vs. enhanced IL-10 suppressogenic response of T-cells upon polyclonal and antigen-specific stimulation. The T-cells from NOD/DR4 Tg mice were unable to induce or suppress diabetes in NOD/RAG deficient mice. This study describes a multifaceted regulatory function of the HLA-DR*0401 allele strongly associated with the lack of T1D development in NOD mice. Published by Elsevier Inc.
机译:已经发现几种人类HLA等位基因与1型糖尿病(T1D)有关,但尚不清楚它们的确切作用。在本文中,我们报告了人类MHC II类(HLA-DR * 0401)等位基因转基因已经表达为易患T1D的NOD(H-2(g7)I-E-null)小鼠,使该小鼠对该病具有抵抗力。 T1D抵抗发生在多点T细胞改变的背景下,例如:(i)CD4 / CD8 T细胞比率偏斜,(ii)CD4(+)CD44(高)T记忆库大小减小,(iii) TCR V beta异常库,(iv)增加Foxp3(+)和TR-1(+)调节细胞的新生儿数量,以及(v)降低IFN-γ炎症反应,而增强T细胞的IL-10抑制原反应多克隆和抗原特异性刺激。来自NOD / DR4 Tg小鼠的T细胞无法诱导或抑制NOD / RAG缺陷小鼠的糖尿病。这项研究描述了HLA-DR * 0401等位基因的多方面调节功能,与NOD小鼠缺乏T1D发育密切相关。由Elsevier Inc.发布

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