Herrera P L, Harlan D M, Fossati L, Izui S, Huarte J, Orci L, Vassalli J D, Vassalli P
Department of Morphology, University of Geneva Medical School, Switzerland.
Diabetologia. 1994 Dec;37(12):1277-9. doi: 10.1007/BF00399802.
While transgenic mice expressing tumour necrosis factor-alpha under the control of the beta-cell-specific insulin promoter display a marked lymphocytic infiltration of the islets, they never develop insulin-dependent diabetes mellitus (IDDM). In striking contrast, "double" transgenic mice whose beta cells express both tumour necrosis factor-alpha as well as the co-stimulatory B7-1 molecule all develop IDDM at an early age. Furthermore, administration of anti-CD8 but not anti-CD4 immunoglobulins prevents diabetes onset. These results indicate that while tumour necrosis factor-alpha induced lymphocytic infiltration is not sufficient to effect beta-cell destruction, locally co-stimulated islet-infiltrating CD8+ T lymphocytes could play a critical role in the development of IDDM.
虽然在β细胞特异性胰岛素启动子控制下表达肿瘤坏死因子-α的转基因小鼠胰岛出现明显的淋巴细胞浸润，但它们从未发展为胰岛素依赖型糖尿病（IDDM）。与之形成鲜明对比的是，β细胞同时表达肿瘤坏死因子-α以及共刺激分子B7-1的“双”转基因小鼠在幼年时都会发展为IDDM。此外，给予抗CD8而不是抗CD4免疫球蛋白可预防糖尿病的发生。这些结果表明，虽然肿瘤坏死因子-α诱导的淋巴细胞浸润不足以导致β细胞破坏，但局部共刺激的胰岛浸润性CD8 + T淋巴细胞可能在IDDM的发展中起关键作用。
