VIRUS-INFECTION TRIGGERS INSULIN-DEPENDENT DIABETES-MELLITUS IN A TRANSGENIC MODEL - ROLE OF ANTI-SELF (VIRUS) IMMUNE-RESPONSE
VIRUS-INFECTION TRIGGERS INSULIN-DEPENDENT DIABETES-MELLITUS IN A TRANSGENIC MODEL - ROLE OF ANTI-SELF (VIRUS) IMMUNE-RESPONSE
复制标题
DOI：
10.1016/0092-8674(91)90165-u
复制
发表时间：
1991-04-19
期刊：
影响因子：
64.5
通讯作者：
LEWICKI, H
中科院分区：
文献类型：
--
作者：
OLDSTONE, MBA;NERENBERG, M;LEWICKI, H
我们通过建立转基因小鼠模型研究了病毒与胰岛素依赖型糖尿病（1型）之间的潜在联系。 通过向这些小鼠中插入独特的病毒蛋白，然后在胰岛中表达为自身抗原，我们可以研究单独或与诱导的抗病毒药物（即，自身免疫性）反应在以后的生活中表现为引起胰岛素依赖型糖尿病。 我们的研究结果表明，早在动物的卵期引入的病毒基因，纳入种系，并在胰岛细胞中表达，当宿主在以后的生活中暴露于相同的病毒时，不会产生耐受性。 我们观察到诱导的抗自身（病毒）CTL应答导致β细胞的选择性和进行性损伤，导致IDDM。
We investigated the potential association between viruses and insulin-dependent (type 1) diabetes (IDDM) by developing a transgenic mouse model. By inserting into these mice a unique viral protein that was then expressed as a self-antigen in the pancreatic islets of Langerhans, we could study the effect on that expressed antigen alone, or in concert with an induced antiviral (i.e., autoimmune) response manifested later in life in causing IDDM. Our results indicate that a viral gene introduced as early as an animal's egg stage, incorporated into the germline, and expressed in islet cells does not produce tolerance when the host is exposed to the same virus later in life. We observed that the induced anti-self (viral) CTL response leads to selective and progressive damage of beta-cells, resulting in IDDM.