INDUCTION AND THERAPY OF AUTOIMMUNE DIABETES IN THE NON-OBESE DIABETIC (NOD/LT) MOUSE BY A 65-KDA HEAT-SHOCK PROTEIN
INDUCTION AND THERAPY OF AUTOIMMUNE DIABETES IN THE NON-OBESE DIABETIC (NOD/LT) MOUSE BY A 65-KDA HEAT-SHOCK PROTEIN
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DOI：
10.1073/pnas.87.4.1576
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发表时间：
1990-02-01
影响因子：
11.1
通讯作者：
COHEN, IR
中科院分区：
文献类型：
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作者：
ELIAS, D;MARKOVITS, D;COHEN, IR
胰岛素依赖型糖尿病是由自身免疫破坏胰腺中产生胰岛素的β细胞引起的。本研究结果表明，非肥胖型糖尿病（NOD/Lt）小鼠的β细胞靶抗原与结核分枝杆菌65-kDa热休克蛋白（hsp65）发生分子交叉反应。β细胞破坏的发生与抗hsp65 T淋巴细胞的自发发展有关。随后，hsp65交叉反应抗原在糖尿病前期小鼠的血清中检测到，几周后，抗hsp65抗体、抗胰岛素抗体和胰岛素抗体中的抗独特型抗体可以检测到。hsp65交叉反应性抗原、自身抗体和t细胞反应性随着胰岛素依赖型糖尿病的发展而下降。抗hsp65 T细胞克隆在年轻NOD/Lt小鼠中引起胰岛素炎和高血糖的能力证实了hsp65在胰岛素依赖型糖尿病发病机制中的重要性。此外，hsp65抗原既可用于诱导糖尿病，也可用于预防糖尿病疫苗，这取决于其对糖尿病前期NOD/Lt小鼠的给药形式。其他抗原如70 kda热休克蛋白（hsp70）对糖尿病的发展没有影响。
Insulin-dependent diabetes mellitus is caused by autoimmune destruction of the insulin-produced beta cells of the pancreas. The results described here indicate that a beta-cell target antigen in non-obese diabetic (NOD/Lt) mice is a molecule cross-reactive with the 65-kDa heat shock protein (hsp65) of Mycobacterium tuberculosis. The onset of beta-cell destruction is associated with the spontaneous development of anti-hsp65 T lymphocytes. Subsequently hsp65 cross-reactive antigen becomes detectable in the sera of the prediabetic mice and some weeks later anti-hsp65 antibodies, anti-insulin antibodies, and anti-idiotypic antibodies in insulin antibodies become detectable. The hsp65-cross-reactive antigen, the autoantibodies, and the T-cell reactivity then decline with the development of overt insulin-dependent diabetes. The importance of hsp65 in the pathogenesis of insulin-dependent diabetes was confirmed by the ability of clones of anti-hsp65 T cells to cause insulitis and hyperglycemia in young NOD/Lt mice. Moreover, hsp65 antigen could be used either to induce diabetes or to vaccinate against diabetes, depending on the form of its administration to prediabetic NOD/Lt mice. Other antigens such as the 70-kDa heat shock protein (hsp70) had no effect on the development of diabetes.