Feige U, van Eden W
Department of Pharmacology, AMGEN Center, Thousand Oaks, CA, USA.
EXS. 1996;77:359-73. doi: 10.1007/978-3-0348-9088-5_24.
Studies of the immune response of mammals to infectious agents have revealed that members of the hsp60 and hsp 70 family are highly immunodominant. Given their high conservation during evolution this was surprising, because of the apparent risk of triggering of autoimmunity and autoimmune disease during the defense of a mammal against infection. However, detailed studies of the immune responses to HSP in models of autoimmune diseases in animals resulted in a change of the view that autoimmunity necessarily leads to autoimmune disease. It has been found that modulation of autoimmunity to HSP is one way to prevent autoimmune disease. At least in some cases even treatment of autoimmune diseases by immunization with heat shock protein appears feasible. This was shown in adjuvant arthritis in Lewis rats and insulin dependent diabetes in NOD mice. Hsp60 and hsp70 are ubiquitous proteins. Their involvement in regulatory loops of autoimmunity may serve as basis for the development of strategies, to prevent and/or treat autoimmune diseases even without knowledge of the causative (auto-)antigen.
对哺乳动物针对感染因子的免疫反应的研究表明,热休克蛋白60(hsp60)和热休克蛋白70(hsp70)家族成员具有高度免疫显性。鉴于它们在进化过程中的高度保守性,这一现象令人惊讶,因为在哺乳动物抵御感染的过程中,存在引发自身免疫和自身免疫性疾病的明显风险。然而,在动物自身免疫性疾病模型中对热休克蛋白免疫反应的详细研究,导致了对自身免疫必然导致自身免疫性疾病这一观点的改变。已发现调节对热休克蛋白的自身免疫是预防自身免疫性疾病的一种方法。至少在某些情况下,用热休克蛋白进行免疫接种治疗自身免疫性疾病似乎是可行的。这在刘易斯大鼠的佐剂性关节炎和非肥胖糖尿病(NOD)小鼠的胰岛素依赖型糖尿病中得到了证实。热休克蛋白60和热休克蛋白70是普遍存在的蛋白质。它们参与自身免疫调节回路,这可能为制定策略奠定基础,即使在不知道致病(自身)抗原的情况下,也能预防和/或治疗自身免疫性疾病。