Fierz W
Schweiz Med Wochenschr. 1987 Mar 14;117(11):391-8.
Chronic debilitating diseases such as multiple sclerosis, demyelinating inflammatory polyradiculoneuropathy, rheumatoid arthritis, diabetes mellitus type I, Hashimoto thyroiditis, forms of uveitis and interstitial nephritis, share many characteristics. They are all organ-specific inflammatory diseases of unknown etiology but with strong evidence of tissue-destructive activity of the cellular immune system in the organs respectively affected, i.e. the central or peripheral nervous system, the joints, the islets of Langerhans, the thyroid gland, the retina, or the tubulo-interstitial renal tissue. Recognized animal models of all these diseases are experimentally induced autoimmune conditions that are transferable with autoreactive T-lymphocytes, in contrast to autoantibodies in humoral autoimmune diseases. In recent years, disease-transferring T-lymphocytes, have been successfully grown as lines and clones in vitro, thus finally proving the primary pathogenic role of autoreactive T-lymphocytes in these animal models. Such T-cell lines are valuable tools in further defining autoantigens, studying mechanisms of T-cell activation in vitro, following T-cell migration and organ-specific homing in vivo, and analyzing effector functions in the infiltrated organs. In addition, questions concerning the breakdown of immunological selftolerance and the basic principles of resistance to disease can be addressed, and possibilities of treatment can be approached. Although the basic etiology of the human organ-specific immune diseases is still unknown, these animal models have helped to throw light on some of the pathogenic mechanisms common to these various diseases.
诸如多发性硬化症、脱髓鞘性炎性多神经根神经病、类风湿性关节炎、I型糖尿病、桥本甲状腺炎、葡萄膜炎和间质性肾炎等慢性衰弱性疾病具有许多共同特征。它们都是病因不明的器官特异性炎性疾病,但有充分证据表明,在分别受影响的器官,即中枢或外周神经系统、关节、胰岛、甲状腺、视网膜或肾小管间质肾组织中,细胞免疫系统具有组织破坏活性。所有这些疾病公认的动物模型都是实验性诱导的自身免疫性疾病,可通过自身反应性T淋巴细胞进行转移,这与体液自身免疫性疾病中的自身抗体不同。近年来,可转移疾病的T淋巴细胞已在体外成功培养成系和克隆,从而最终证明了自身反应性T淋巴细胞在这些动物模型中的主要致病作用。此类T细胞系是进一步确定自身抗原、研究体外T细胞激活机制、追踪体内T细胞迁移和器官特异性归巢以及分析浸润器官中效应功能的宝贵工具。此外,还可以探讨有关免疫自身耐受破坏和抗病基本原则的问题,以及治疗的可能性。尽管人类器官特异性免疫疾病的基本病因仍然不明,但这些动物模型有助于阐明这些不同疾病共有的一些致病机制。