Induction of tolerance in murine autoimmune diabetes by transient blockade of leukocyte function-associated antigen-1/intercellular adhesion molecule-1 pathway.
Induction of tolerance in murine autoimmune diabetes by transient blockade of leukocyte function-associated antigen-1/intercellular adhesion molecule-1 pathway.
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通过短暂阻断白细胞功能相关抗原 1/细胞间粘附分子 1 途径诱导小鼠自身免疫性糖尿病耐受。
DOI：
10.4049/jimmunol.157.8.3737
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发表时间：
1996
影响因子：
4.4
通讯作者：
M. Kasuga
中科院分区：
文献类型：
--
作者：
H. Moriyama;K. Yokono;K. Amano;M. Nagata;Y. Hasegawa;N. Okamoto;K. Tsukamoto;M. Miki;R. Yoneda;N. Yagi;Y. Tominaga;H. Kikutani;K. Hioki;K. Okumura;H. Yagita;M. Kasuga
本研究表明，在关键时期短期给予抗白细胞功能相关抗原-1（LFA-1）和细胞间粘附分子-1（ICAM-1）的mAb可完全保护非肥胖糖尿病（NOD）小鼠的自身免疫性糖尿病。当这些mAb在2周龄时仅给药6天时，在30周龄时既未观察到糖尿病也未观察到胰岛炎。似乎对β细胞Ag（s）的耐受性是由LFA-1/ICAM-1途径的这种瞬时阻断诱导的。保护性抑制活性不足以预防糖尿病，因为从2周龄时接受这些mAb的雌性NOD小鼠共转移脾细胞，仅导致急性糖尿病NOD小鼠脾细胞过继转移引起的糖尿病发作的短暂延迟。这些脾细胞转移到年轻的NOD小鼠也不能消除自发性糖尿病和胰岛炎。环磷酰胺处理不能消除这种保护作用。当将来自经治疗的NOD小鼠的脾细胞转移至NOD-SCID小鼠时，受体小鼠均未发生显著的胰岛炎和随后的明显糖尿病，表明致糖尿病效应T细胞的缺失或失活。然而，接受mAb治疗的无胰岛炎NOD小鼠的脾T细胞在体外保留了对胰岛细胞和65 kDa谷氨酸脱羧酶（GAD 65）的增殖反应。这些结果表明，一个独特的外周耐受诱导的LFA-1/ICAM-1通路的短暂封锁在早期年龄的NOD小鼠。
The present study demonstrated that a short-term administration of mAbs against leukocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) at critical periods resulted in complete protection of autoimmune diabetes in non-obese diabetic (NOD) mice. When these mAbs were administered for only 6 days at 2 wk of age, neither diabetes nor insulitis was observed at 30 wk of age. It appears that the tolerance against beta cell Ag(s) was induced by this transient blockade of the LFA-1/ICAM-1 pathway. Protective suppressor activity was not enough to prevent diabetes because co-transfer of splenocytes from female NOD mice, which had received these mAbs at 2 wk of age, resulted in only a short delay of the diabetic onset caused by adoptive transfer of splenocytes from acutely diabetic NOD mice. Transfer of these splenocytes to young NOD mice could not also abrogate the spontaneous diabetes and insulitis. Furthermore, cyclophosphamide treatment could not abrogate the protection. When splenocytes from the treated NOD mice were transferred to NOD-SCID mice, none of the recipient mice developed significant insulitis and subsequent overt diabetes, suggesting the absence or the inactivation of diabetogenic effector T cells. However, splenic T cells from the insulitis-free NOD mice that had received the mAb treatment preserved proliferative responses to both islet cells and 65-kDa glutamic acid decarboxylase (GAD65) in vitro. These results suggest that a unique peripheral tolerance was induced by the transient blockade of the LFA-1/ICAM-1 pathway in an early age of NOD mice.