Larger E, Bécourt C, Bach J F, Boitard C
Institut National de la Recherche Médicale U 25, Hôpital Necker, Paris, France.
J Exp Med. 1995 May 1;181(5):1635-42. doi: 10.1084/jem.181.5.1635.
The role of autoantigens and that of target organs in which tissue lesions develop remains elusive in most spontaneous models of autoimmune diseases. Whether the presence of target autoantigens is required for the recruitment of autoreactive lymphocytes is unknown in most cases. To evaluate the importance of islet cells in the development of autoimmunity in the nonobese diabetic (NOD) mouse, we generated beta cell-deprived mice by injecting a high dose of alloxan, a toxic agent specific for beta cells. In contrast with spleen cells from 6-mo-old naive NOD mice which transfer diabetes in irradiated 8-mo-old male recipients, spleen cells from age-matched NOD mice which received a single injection of alloxan at 3 wk of age did not transfer diabetes. With the exception of the ability to transfer diabetes, beta cell-deprived NOD mice showed maintained immune competence. Furthermore, sialitis developed with the expected intensity and prevalence in beta cell-deprived mice. Already committed "diabetogenic" spleen cells collected from spontaneously diabetic mice also showed a reduced capacity to transfer diabetes after their removal from the diabetic mice and transient "parking" in beta cell-deprived mice. Taken together, our data bring evidence that involvement of autoreactive T cells detected by the capacity to transfer diabetes requires the presence of target beta cells.
在大多数自身免疫性疾病的自发模型中，自身抗原的作用以及发生组织损伤的靶器官的作用仍不清楚。在大多数情况下，自身反应性淋巴细胞的募集是否需要靶自身抗原的存在尚不清楚。为了评估胰岛细胞在非肥胖糖尿病（NOD）小鼠自身免疫发展中的重要性，我们通过注射高剂量的四氧嘧啶（一种对β细胞有特异性的毒性剂）来生成β细胞缺失的小鼠。与6月龄未接触过抗原的NOD小鼠的脾细胞（能使受照射的8月龄雄性受体患糖尿病）不同，3周龄时接受单次四氧嘧啶注射的年龄匹配的NOD小鼠的脾细胞不能使受体患糖尿病。除了转移糖尿病的能力外，β细胞缺失的NOD小鼠表现出维持的免疫能力。此外，β细胞缺失的小鼠中涎腺炎以预期的强度和发生率发展。从自发糖尿病小鼠收集的已致敏的“致糖尿病”脾细胞，在从糖尿病小鼠中取出并短暂“寄养”在β细胞缺失的小鼠后，转移糖尿病的能力也降低。综上所述，我们的数据证明，通过转移糖尿病的能力检测到的自身反应性T细胞的参与需要靶β细胞的存在。
