PREVENTION OF AUTOIMMUNE INSULITIS IN NONOBESE DIABETIC MICE BY EXPRESSION OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I LD-MOLECULES
PREVENTION OF AUTOIMMUNE INSULITIS IN NONOBESE DIABETIC MICE BY EXPRESSION OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I LD-MOLECULES
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DOI：
10.1073/pnas.89.20.9519
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发表时间：
1992-10-15
影响因子：
11.1
通讯作者：
YAMAMURA, K
中科院分区：
文献类型：
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作者：
MIYAZAKI, T;MATSUDA, Y;YAMAMURA, K
非肥胖糖尿病 (NOD) 小鼠会自发地患上 T 细胞介导的自身免疫性疾病，该疾病在许多方面与人类胰岛素依赖型糖尿病相似。 NOD 小鼠表达主要组织相容性复合物 I 类 K(d) 和 D(b) 抗原。为了研究主要组织相容性复合物 I 类分子在自身免疫性胰岛素炎发展中的可能参与，我们尝试通过将 I 类 L(d) 基因转基因的 C57BL/6 小鼠与 NOD 小鼠杂交，在 NOD 小鼠中表达不同类型的 I 类分子。回交后代在外周血淋巴细胞上表达L(d)抗原，其水平与BALB/c小鼠相当。外周血淋巴细胞上内源性I类和II类抗原的细胞表面表达不受影响。对这些小鼠的分析表明，II 类 L(d) 抗原的表达显着降低了 20 周龄时的胰岛素炎发病率。小鼠染色体上生物素化探针的原位杂交表明，L(d) 转基因位于 6 号染色体的 E 区，与胰岛素依赖性糖尿病没有遗传联系。这些结果表明，NOD 型 I 类分子参与 NOD 小鼠胰岛素炎的发生。
Nonobese diabetic (NOD) mice spontaneously develop a T-cell-mediated autoimmune disease that is similar in many respects to insulin-dependent diabetes mellitus in humans. NOD mice were shown to express major histocompatibility complex class I K(d) and D(b) antigens. To examine the possible involvement of major histocompatibility complex class I molecules in the development of autoimmune insulitis, we attempted to express a different type of class I molecule in NOD mice by crossing C57BL/6 mice transgenic for the class I L(d) gene with NOD mice. The backcross progeny expressed the L(d) antigen on the peripheral blood lymphocytes at a level comparable with that of the BALB/c mice. The cell surface expression of endogenous class I and class II antigens on the peripheral blood lymphocytes was not affected. Analysis of these mice revealed that the expression of the class I L(d) antigen significantly reduced the incidence of insulitis at 20 weeks of age. In situ hybridization of a biotinylated probe on mouse chromosomes showed that the L(d) transgene was located in the E area of chromosome 6 with which no genetic linkage to insulin-dependent diabetes mellitus was demonstrated. These results suggest that the NOD-type class I molecules are involved in the development of insulitis in NOD mice.