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口服髓鞘碱性蛋白对实验性自身免疫性脑脊髓炎的抑制作用。V. 不同物种来源的髓鞘碱性蛋白的抑制作用层级

Suppression of experimental autoimmune encephalomyelitis by oral administration of myelin basic protein. V. Hierarchy of suppression by myelin basic protein from different species.

作者信息

Miller A, Lider O, al-Sabbagh A, Weiner H L

机构信息

Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115.

出版信息

J Neuroimmunol. 1992 Aug;39(3):243-50. doi: 10.1016/0165-5728(92)90258-m.

Abstract

We have been investigating the suppression of experimental autoimmune encephalomyelitis (EAE) by oral tolerization to autoantigens. In the present study the tolerizing effect of orally administered myelin basic protein (MBP) from different species was examined in the Lewis rat, Hartley guinea pig, and SJL/J mouse model of EAE. Animals were fed guinea pig, rat, bovine, human or mouse-MBP and then immunized with the homologous species of MBP or myelin: Lewis rats were immunized with rat MBP, Hartley guinea pigs with guinea pig-MBP, and SJL/J mice with mouse myelin. Clinical expression of EAE and delayed-type hypersensitivity (DTH) responses to MBP were assessed. In each species, suppression of disease and DTH responses were most pronounced by tolerization with the homologous species of MBP. In addition, cross-species tolerization was observed in each species and in general was less suppressive than homologous MBP although in some instances MBP from a heterologous species was as effective as tolerization with the homologous species. We also studied guinea pig-MBP induced EAE in the Lewis rat because it is a widely studied model of EAE and found that oral tolerization with guinea pig MBP was as suppressive as rat MBP. Of note is that oral tolerization with mouse MBP suppressed myelin-induced EAE in the SJL mouse in which autoimmunity to proteolipid protein appears to play a primary role, suggesting that antigen-driven bystander suppression following oral tolerization with autoantigens (Miller et al., 1991b) may be an important contributing mechanism for suppression of EAE following oral tolerization with MBP in this model.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

我们一直在研究通过对自身抗原进行口服耐受来抑制实验性自身免疫性脑脊髓炎(EAE)。在本研究中,我们在Lewis大鼠、Hartley豚鼠和SJL/J小鼠EAE模型中检测了口服不同物种髓鞘碱性蛋白(MBP)的耐受效果。给动物喂食豚鼠、大鼠、牛、人或小鼠的MBP,然后用同源物种的MBP或髓磷脂进行免疫:Lewis大鼠用大鼠MBP免疫,Hartley豚鼠用豚鼠MBP免疫,SJL/J小鼠用小鼠髓磷脂免疫。评估了EAE的临床症状以及对MBP的迟发型超敏反应(DTH)。在每个物种中,用同源物种的MBP进行耐受时,疾病和DTH反应的抑制最为明显。此外,在每个物种中都观察到了跨物种耐受,总体而言其抑制作用比同源MBP弱,尽管在某些情况下,异源物种的MBP与同源物种的耐受效果一样有效。我们还研究了豚鼠MBP在Lewis大鼠中诱导的EAE,因为这是一个被广泛研究的EAE模型,发现用豚鼠MBP进行口服耐受与大鼠MBP的抑制效果相同。值得注意的是,用小鼠MBP进行口服耐受可抑制SJL小鼠中髓磷脂诱导的EAE,在该小鼠中对蛋白脂蛋白的自身免疫似乎起主要作用,这表明在用自身抗原进行口服耐受后抗原驱动的旁观者抑制(Miller等人,1991b)可能是该模型中用MBP进行口服耐受后抑制EAE的一个重要促成机制。(摘要截短至250字)

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