Expression of transgene encoded TGF-β in islets prevents autoimmune diabetes in NOD mice by a local mechanism
Expression of transgene encoded TGF-β in islets prevents autoimmune diabetes in NOD mice by a local mechanism
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DOI：
10.1006/jaut.2002.0599
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发表时间：
2002-08-01
影响因子：
12.8
通讯作者：
Flavell, RA
中科院分区：
文献类型：
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作者：
Grewal, IS;Grewal, KD;Flavell, RA
为了分析TGF-β在胰岛素依赖型糖尿病（IDDM）中的作用，我们开发了在大鼠胰岛素II启动子控制下表达TGF-β的非肥胖糖尿病（NOD）转基因小鼠。TGF-β转基因小鼠的胰腺大约是野生型NOD小鼠胰腺大小的二十分之一，并且显示出小的微胰岛簇，而不是正常的成年胰岛。然而，这些胰岛产生足够水平的胰岛素以维持正常的葡萄糖水平，并且小鼠免受糖尿病的影响，糖尿病在其阴性同窝出生的小鼠中发展。在转基因胰腺中观察到大量的纤维化，伴随着单核细胞的浸润，随着年龄的增长而减少。有趣的是，这些小鼠在其脾脏中显示出正常的抗胰岛免疫应答，并且仍然对成熟克隆的CD 8效应细胞过继转移的IDDM敏感。TUNEL检测显示，与非转基因NOD小鼠相比，入侵细胞的凋亡增加。总之，这些结果表明TGF-β通过局部事件保护胰岛。(C)2002爱思唯尔科技有限公司版权所有。
To analyse the effects of TGF-beta in insulin dependent diabetes mellitus (IDDM), we have developed non-obese diabetic (NOD) transgenic mice expressing TGF-beta under the control of the rat insulin II promoter. Pancreata of TGF-beta transgenic mice were roughly one twentieth of the size of pancreata of wild-type NOD mice and showed small clusters of micro-islets rather than normal adult islets. However, these islets produced sufficient levels of insulin to maintain normal glucose levels and mice were protected from the diabetes, which developed in their negative littermates. A massive fibrosis was seen in the transgenic pancreata that was accompanied with infiltration of mononuclear cells that decreased with age. Interestingly, these mice showed normal anti-islet immune response in their spleens and remained susceptible to adoptive transfer of IDDM by mature cloned CD8 effector cells. TUNEL assays revealed increased apoptosis of invading cells when compared to non-transgenic NOD mice. Taken together, these results suggest that TGF-beta protects islets by a local event. (C) 2002 Elsevier Science Ltd. All rights reserved.