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首页> 外文期刊>Clinical immunology: The official journal of the Clinical Immunology Society >Age-dependent loss of tolerance to an immunodominant epitope of glutamic acid decarboxylase in diabetic-prone RIP-B7/DR4 mice.
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Age-dependent loss of tolerance to an immunodominant epitope of glutamic acid decarboxylase in diabetic-prone RIP-B7/DR4 mice.

机译：糖尿病易感RIP-B7 / DR4小鼠对谷氨酸脱羧酶免疫显性表位的耐受性随年龄的增长而下降。

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摘要

We have identified for the first time an age-dependent spontaneous loss of tolerance to two self-antigenic epitopes derived from putative diabetes-associated antigens glutamic acid decarboxylase (GAD65) and glial fibrillary acidic protein (GFAP) in RIP-B7/DRB1*0404 HLA transgenic mice. Diabetic and older non-diabetic mice exhibited a proliferative response to an immunodominant epitope from GAD65 (555-567) and also from GFAP (240-252) but not from an immunogenic epitope from diabetes-associated islet-specific glucose-6-phosphatase catalytic subunit-related protein. The response to both of these self-antigens is not observed in young mice but is observed in older non-diabetic mice and is accompanied by histological evidence of insulitis in the absence of overt diabetes. Islet infiltrates in older non-diabetic mice and diabetic mice contain CD4(+)/FoxP3(+) cells and suggest the presence of a regulatory mechanism prior and during diabetic disease. Diabetes penetrance in RIP-B7/DR0404 mice is 23% with a mean onset age of 40 weeks and is similar to that reported for RIP-B7/DR0401 mice. A gender preference is observed in that 38% of female mice become diabetic compared to 8% of male mice.
机译：我们首次在RIP-B7 / DRB1 * 0404中首次发现了与年龄有关的自发性耐受力，这些耐受性来自于两个与糖尿病相关的抗原谷氨酸脱羧酶（GAD65）和神经胶质纤维酸性蛋白（GFAP）衍生的自体抗原表位HLA转基因小鼠。糖尿病和老年非糖尿病小鼠对GAD65（555-567）和GFAP（240-252）的免疫显性表位表现出增殖反应，但对糖尿病相关的胰岛特异性葡萄糖-6-磷酸酶催化的免疫原性表位没有反应亚基相关蛋白。在年幼的小鼠中未观察到对这两种自身抗原的反应，但在年长的非糖尿病小鼠中却观察到了这两种反应，并且在没有明显的糖尿病的情况下伴有组织炎性炎的证据。在较老的非糖尿病小鼠和糖尿病小鼠中，胰岛浸润含有CD4（+）/ FoxP3（+）细胞，提示在糖尿病疾病发生之前和之中存在调节机制。 RIP-B7 / DR0404小鼠的糖尿病外显率为23％，平均发病年龄为40周，与RIP-B7 / DR0401小鼠的糖尿病外显率相似。观察到性别偏好，因为38％的雌性小鼠患有糖尿病，而8％的雄性小鼠患有糖尿病。

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