Hauet-Broere F, Wieten L, Guichelaar T, Berlo S, van der Zee R, Van Eden W
Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, Yalelaan 1, 3584CL, the Netherlands.
Ann Rheum Dis. 2006 Nov;65 Suppl 3(Suppl 3):iii65-8. doi: 10.1136/ard.2006.058495.
The significance of immune responses to certain heat shock proteins (HSPs) that develop in virtually all inflammatory diseases is only now becoming clear. In experimental models, HSPs prevent or arrest inflammatory damage, and initial clinical trials in chronic inflammatory disease have shown HSP peptides to promote production of anti-inflammatory cytokines-indicating immunoregulatory potential. HSPs are ubiquitous self-antigens that are highly expressed in inflamed tissues. The prokaryotic homologous proteins, present in every bacterial species, are dominantly immunogenic. This is striking, especially as these proteins have large areas of sequence homologies with the host (mammalian) counterparts. In several experimental models of autoimmune diseases, immunisation with bacterial HSPs inhibited disease development, as did oral/nasal administration. Based on the experimental evidence so far, it is tempting to speculate that: firstly, exposure to homologues of these self-antigens, as present in, for instance, the bacterial intestinal flora, has a decisive impact on the regulation of self-tolerance at the level of T cells; and secondly, such proteins or their derivative peptides may have a role in an antigen specific immunotherapy approach involving modulation of relevant T cells, without the immediate necessity of defining disease specific autoantigens. Recent findings in experimental asthma and atherosclerosis have indicated that the field of application of such immunotherapy can be broader than just autoimmunity.
几乎在所有炎症性疾病中都会产生的针对某些热休克蛋白（HSPs）的免疫反应，其重要性直到现在才逐渐明晰。在实验模型中，热休克蛋白可预防或阻止炎症损伤，并且针对慢性炎症性疾病的初步临床试验表明，热休克蛋白肽可促进抗炎细胞因子的产生，这表明其具有免疫调节潜力。热休克蛋白是普遍存在的自身抗原，在炎症组织中高度表达。存在于每种细菌中的原核同源蛋白具有主要的免疫原性。这一点很显著，尤其是因为这些蛋白与宿主（哺乳动物）对应物有大片的序列同源性。在几种自身免疫性疾病的实验模型中，用细菌热休克蛋白进行免疫可抑制疾病发展，口服/鼻内给药也有同样效果。基于目前的实验证据，很容易推测：首先，接触这些自身抗原的同源物，比如存在于肠道细菌菌群中的同源物，会对T细胞水平的自身耐受性调节产生决定性影响；其次，这类蛋白或其衍生肽可能在涉及调节相关T细胞的抗原特异性免疫治疗方法中发挥作用，而无需立即确定疾病特异性自身抗原。实验性哮喘和动脉粥样硬化的最新研究结果表明，这种免疫治疗的应用领域可能比自身免疫性疾病更广泛。
