The 60-kDa heat shock protein modulates allograft rejection
The 60-kDa heat shock protein modulates allograft rejection
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DOI：
10.1073/pnas.96.9.5159
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发表时间：
1999-04-27
影响因子：
11.1
通讯作者：
Cohen, IR
中科院分区：
文献类型：
--
作者：
Birk, OS;Gur, SL;Cohen, IR
同种异体移植排斥反应是由外来移植抗原引发的免疫反应过程。我们现在证明，60 kDa的热休克蛋白（hsp 60），一个分子，是相同的供体和受体，可以调节同种异体移植免疫。在野生型小鼠中，hsp 60的表达在被排斥的同种异体移植物中大大增强。通过使用MHC II类（E-alpha）启动子hsp 60转基因小鼠作为供体的皮肤与增强表达的hsp 60，或作为同种异体移植受体与减少hsp 60自身免疫，我们发现，增强表达的小鼠hsp 60在同种异体移植加速其排斥反应，而减少自身免疫小鼠hsp 60在移植受体延迟的过程。此外，在非转基因小鼠中，已知调节天然存在的hsp 60自身免疫的hsp 60或hsp 60肽的治疗性给药导致延迟的同种异体移植物排斥。因此，我们证明，热休克蛋白60的表达和热休克蛋白60自身免疫可以影响和修改对外来抗原的免疫反应。因此，对自身热休克蛋白60表位的自身免疫不一定是一种畸变，但可以在生理和治疗上调节外源免疫。
Allograft rejection is a process of immune reactivity triggered by foreign transplantation antigens. We now demonstrate that the 60-kDa heat shock protein (hsp60), a molecule that is identical in the donor and the recipient, can regulate allograft immunity. In wild-type mice, hsp60 expression was greatly enhanced in allografts being rejected. By using MHC class II (E-alpha) promoter hsp60 transgenic mice either as donors of skin with enhanced expression of hsp60, or as allograft recipients with decreased hsp60 autoimmunity, we found that augmented expression of mouse hsp60 in the allograft accelerated its rejection, whereas reduced autoimmunity to mouse hsp60 in graft recipients delayed the process. Moreover, in nontransgenic mice, therapeutic administration of hsp60 or hsp60 peptides, known to modulate naturally occurring hsp60 autoimmunity, led to delayed allograft rejection. Thus, we demonstrate that hsp60 expression and hsp60 autoimmunity can influence and modify the immune response to foreign antigens. Hence, autoimmunity to self-hsp60 epitopes is not necessarily an aberration, but may serve physiologically and therapeutically to modulate foreign immunity.