GENETIC REQUIREMENTS FOR ACCELERATION OF DIABETES IN NONOBESE DIABETIC MICE EXPRESSING INTERLEUKIN-2 IN ISLET BETA-CELLS
GENETIC REQUIREMENTS FOR ACCELERATION OF DIABETES IN NONOBESE DIABETIC MICE EXPRESSING INTERLEUKIN-2 IN ISLET BETA-CELLS
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DOI：
10.1002/eji.1830241041
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发表时间：
1994-10-01
影响因子：
5.4
通讯作者：
MILLER, JFAP
中科院分区：
文献类型：
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作者：
ALLISON, J;MCCLIVE, P;MILLER, JFAP
在β细胞中表达白细胞介素-2（IL-2）的非肥胖糖尿病（NOD）转基因小鼠中，糖尿病显著加速。与C57 BL/6的单交完全阻止了这种效应，进一步与NOD遗传背景的回交表明，糖尿病加速需要至少两个糖尿病易感基因座（Idd 1 s和Idd 3/10 s）。活化为胰岛抗原的T细胞不在小鼠体内循环。IL-2的加速作用在缺乏CD 8（+）T细胞的NOD小鼠和NOD SCID小鼠中存在，但降低。这意味着在NOD遗传背景下，胰岛特异性CD 4（+）T细胞产生细胞因子（如IL-2）可导致β细胞损伤和糖尿病，而CD 8（+）T细胞可能在加速糖尿病发作中发挥作用。
Diabetes was dramatically accelerated in non-obese diabetic (NOD) transgenic mice that expressed interleukin-2 (IL-2) in their beta cells. A single cross to C57BL/6 completely prevented this effect and a further backcross to the NOD genetic background showed that at least two diabetes susceptibility loci (Idd1s and Idd3/10s) were required for the diabetes acceleration. T cells activated to islet antigens were not circulating in the mice. The accelerating effect of IL-2 was present, but decreased, in NOD mice that lacked CD8(+) T cells as well as in NOD SCID mice. The implications are that in the NOD genetic background, the production of cytokines, such as IL-2, by islet-specific CD4(+) T cells can lead to beta cell damage and diabetes and that CD8(+) T cells may have a role in accelerating diabetes onset.