Elias D, Markovits D, Reshef T, van der Zee R, Cohen I R
Department of Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Proc Natl Acad Sci U S A. 1990 Feb;87(4):1576-80. doi: 10.1073/pnas.87.4.1576.
Insulin-dependent diabetes mellitus is caused by autoimmune destruction of the insulin-producing 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 to 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.
胰岛素依赖型糖尿病是由胰腺中产生胰岛素的β细胞的自身免疫性破坏引起的。此处所述结果表明，非肥胖型糖尿病（NOD/Lt）小鼠中的一种β细胞靶抗原是一种与结核分枝杆菌65 kDa热休克蛋白（hsp65）交叉反应的分子。β细胞破坏的开始与抗hsp65 T淋巴细胞的自发发展有关。随后，在糖尿病前期小鼠的血清中可检测到hsp65交叉反应抗原，几周后可检测到抗hsp65抗体、抗胰岛素抗体以及针对胰岛素抗体的抗独特型抗体。随着显性胰岛素依赖型糖尿病的发展，hsp65交叉反应抗原、自身抗体和T细胞反应性会下降。抗hsp65 T细胞克隆在年轻的NOD/Lt小鼠中引发胰岛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，根据对糖尿病前期NOD/Lt小鼠的给药形式，hsp65抗原既可以用来诱发糖尿病，也可以用来接种预防糖尿病。其他抗原，如70 kDa热休克蛋白（hsp70），对糖尿病的发展没有影响。
