Oldstone M B, Nerenberg M, Southern P, Price J, Lewicki H
Department of Neuropharmacology, Scripps Clinic and Research Foundation, La Jolla, California 92037.
Cell. 1991 Apr 19;65(2):319-31. doi: 10.1016/0092-8674(91)90165-u.
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.
我们通过建立转基因小鼠模型来研究病毒与胰岛素依赖型（1型）糖尿病（IDDM）之间的潜在关联。通过将一种独特的病毒蛋白插入这些小鼠体内，该蛋白随后在胰岛中作为自身抗原表达，我们可以单独研究对该表达抗原的影响，或者与生命后期出现的诱导抗病毒（即自身免疫）反应共同作用，以引发IDDM。我们的结果表明，早在动物的卵期引入并整合到种系中并在胰岛细胞中表达的病毒基因，在宿主生命后期接触相同病毒时不会产生耐受性。我们观察到，诱导的抗自身（病毒）CTL反应会导致β细胞的选择性和进行性损伤，从而导致IDDM。
