Acquired tolerance to experimental autoimmune encephalomyelitis by intrathymic injection of myelin basic protein or its major encephalitogenic peptide.
Acquired tolerance to experimental autoimmune encephalomyelitis by intrathymic injection of myelin basic protein or its major encephalitogenic peptide.
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DOI：
10.1084/jem.178.2.559
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发表时间：
1993-08-01
期刊：
影响因子：
--
通讯作者：
Weiner HL
中科院分区：
文献类型：
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作者：
Khoury SJ;Sayegh MH;Hancock WW;Gallon L;Carpenter CB;Weiner HL
实验性自身免疫性脑脊髓炎（Experimental autoimmune encephalomyelitis，EAE）是一种中枢神经系统的炎性疾病，可通过髓鞘碱性蛋白（myelin basic protein，MBP）佐剂免疫在许多物种中诱导，并可作为研究多发性硬化的实验模型。胸腺在自身免疫模型中获得性耐受中的作用尚未得到彻底研究。本研究观察了胸腺内注射MBP或其主要致脑炎肽对刘易斯大鼠EAE病程的影响。在免疫前48小时（而非免疫后）单次胸腺内注射MBP可保护动物免受主动诱导的EAE。一个完整的MBP引发的胸腺需要长达10天postmunization，胸腺切除术后第1，2和7天postmunization废除的保护作用，而胸腺切除术在第10天没有。在胸腺内注射MBP的动物中，引发的淋巴细胞的增殖反应显着降低。对临床EAE的保护作用是通过胸腺注射致脑炎的主要区域（残基71-90）而不是非致脑炎的（21-40）MBP表位诱导的。免疫组织学检查从大鼠胸腺内注射致脑炎肽的大脑显示显着减少细胞浸润和激活和炎性细胞因子的虚拟情况下，与大鼠胸腺内注射nonencephalitogenic肽。这些结果表明，胸腺可能在T细胞介导的实验性自身免疫性疾病的获得性系统免疫耐受中发挥积极作用。这种效应可能是通过胸腺循环的自身反应性T细胞克隆的克隆失活过程介导的。
Experimental autoimmune encephalomyelitis (EAE) is an inflammatory disease of the central nervous system that can be induced in a number of species by immunization with myelin basic protein (MBP) in adjuvant, and serves as an experimental model for the study of multiple sclerosis. The role of the thymus in acquired tolerance in autoimmune models has not been thoroughly investigated. In this study, we examined the effects of intrathymic injection of MBP or its major encephalitogenic peptide on the course of EAE in Lewis rats. A single intrathymic injection of MBP 48 h pre- but not postimmunization protects animals from actively induced EAE. An intact MBP-primed thymus was required up to 10 d postimmunization, as thymectomy on days 1, 2, and 7 postimmunization abrogated the protective effect, whereas thymectomy on day 10 did not. The proliferative response of primed lymphocytes was significantly reduced in animals that were intrathymically injected with MBP. Protection against clinical EAE was induced by thymic injection of the major encephalitogenic region (residues 71-90) but not a nonencephalitogenic (21-40) MBP epitope. Immunohistologic examination of the brain from rats intrathymically injected with encephalitogenic peptide showed markedly reduced cellular infiltrate and virtual absence of activation and inflammatory cytokines as compared with rats intrathymically injected with the nonencephalitogenic peptide. These results indicate that the thymus may play an active role in acquired systemic immunologic tolerance in T cell-mediated experimental autoimmune diseases. This effect may be mediated by a process of clonal inactivation of autoreactive T cell clones circulating through the thymus.