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通过致糖尿病性CD4+ T细胞的过继转移在小鼠中加速1型糖尿病的诱导。

Accelerated type 1 diabetes induction in mice by adoptive transfer of diabetogenic CD4+ T cells.

作者信息

Berry Gregory, Waldner Hanspeter

机构信息

Department of Microbiology & Immunology, Pennsylvania State University College of Medicine, USA.

出版信息

J Vis Exp. 2013 May 6(75):e50389. doi: 10.3791/50389.

Abstract

The nonobese diabetic (NOD) mouse spontaneously develops autoimmune diabetes after 12 weeks of age and is the most extensively studied animal model of human Type 1 diabetes (T1D). Cell transfer studies in irradiated recipient mice have established that T cells are pivotal in T1D pathogenesis in this model. We describe herein a simple method to rapidly induce T1D by adoptive transfer of purified, primary CD4+ T cells from pre-diabetic NOD mice transgenic for the islet-specific T cell receptor (TCR) BDC2.5 into NOD.SCID recipient mice. The major advantages of this technique are that isolation and adoptive transfer of diabetogenic T cells can be completed within the same day, irradiation of the recipients is not required, and a high incidence of T1D is elicited within 2 weeks after T cell transfer. Thus, studies of pathogenesis and therapeutic interventions in T1D can proceed at a faster rate than with methods that rely on heterogenous T cell populations or clones derived from diabetic NOD mice.

摘要

非肥胖糖尿病(NOD)小鼠在12周龄后会自发发展为自身免疫性糖尿病,是研究最为广泛的人类1型糖尿病(T1D)动物模型。对受辐照受体小鼠进行的细胞转移研究表明,T细胞在该模型的T1D发病机制中起关键作用。我们在此描述一种简单方法,即通过将来自胰岛特异性T细胞受体(TCR)BDC2.5转基因的糖尿病前期NOD小鼠的纯化原代CD4 + T细胞过继转移到NOD.SCID受体小鼠中,快速诱导T1D。该技术的主要优点是致糖尿病T细胞的分离和过继转移可在同一天内完成,无需对受体进行辐照,并且在T细胞转移后2周内可引发高发病率的T1D。因此,与依赖于来自糖尿病NOD小鼠的异质性T细胞群体或克隆的方法相比,T1D发病机制和治疗干预的研究可以更快地进行。

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