Overexpression of natural killer T cells protects Valpha14- Jalpha281 transgenic nonobese diabetic mice against diabetes.
Overexpression of natural killer T cells protects Valpha14- Jalpha281 transgenic nonobese diabetic mice against diabetes.
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DOI：
10.1084/jem.188.10.1831
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发表时间：
1998-11-16
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在非肥胖糖尿病（NOD）小鼠中，破坏性胰岛炎的进展与调节细胞的失败有关，可能涉及辅助性T细胞2型（Th 2）细胞。自然杀伤（NK）T细胞可能参与糖尿病，鉴于其在NOD小鼠中的缺陷和通过过继转移α/β双阴性胸腺细胞预防糖尿病。在这里，我们通过使用表达NK T细胞特征性T细胞抗原受体（TCR）α链Vα14-Jα281的转基因NOD小鼠来评估NK T细胞在糖尿病中的作用。NK1.1+ T细胞的精确鉴定是基于与同类NK1.1 NOD小鼠的异交。所有6个转基因株系均表现出不同程度的NK 1.1 + T细胞数量增加、白细胞介素（IL）-4产生增加和血清免疫球蛋白E水平升高。只有具有最大数量的NK T细胞和最强的IL-4产生爆发的转基因系才能免受糖尿病的影响。用转基因脾细胞进行的转移和共转移实验表明，Vα14-Jα281转基因NOD小鼠虽然没有明显的糖尿病，但产生了致糖尿病性T细胞库，NK T细胞积极抑制T细胞的致病作用。这些结果表明，NK T细胞的数量强烈影响糖尿病的发展。
Progression to destructive insulitis in nonobese diabetic (NOD) mice is linked to the failure of regulatory cells, possibly involving T helper type 2 (Th2) cells. Natural killer (NK) T cells might be involved in diabetes, given their deficiency in NOD mice and the prevention of diabetes by adoptive transfer of α/β double-negative thymocytes. Here, we evaluated the role of NK T cells in diabetes by using transgenic NOD mice expressing the T cell antigen receptor (TCR) α chain Vα14-Jα281 characteristic of NK T cells. Precise identification of NK1.1+ T cells was based on out-cross with congenic NK1.1 NOD mice. All six transgenic lines showed, to various degrees, elevated numbers of NK1.1+ T cells, enhanced production of interleukin (IL)-4, and increased levels of serum immunoglobulin E. Only the transgenic lines with the largest numbers of NK T cells and the most vigorous burst of IL-4 production were protected from diabetes. Transfer and cotransfer experiments with transgenic splenocytes demonstrated that Vα14-Jα281 transgenic NOD mice, although protected from overt diabetes, developed a diabetogenic T cell repertoire, and that NK T cells actively inhibited the pathogenic action of T cells. These results indicate that the number of NK T cells strongly influences the development of diabetes.