Zhu J, Deng G M, Levi M, Wahren B, Diab A, van der Meide P H, Link H
Karolinska Institute, Division of Neurology, Huddinge University Hospital, Stockholm, Sweden.
J Neuropathol Exp Neurol. 1998 Mar;57(3):291-301. doi: 10.1097/00005072-199803000-00010.
Experimental autoimmune neuritis (EAN) is a CD4+ T cell-mediated inflammatory demyelinating disease of the peripheral nervous system (PNS) that serves as a model for Guillain-Barre syndrome (GBS) in humans. Both EAN and GBS are associated with upregulated T and B cells responses to PNS myelin proteins including P2 protein, and by changes of the Th1/Th2 cell balance in favor of Th1. Here we report that EAN can be prevented by the dominant neuritogenic peptide 57-81 of the PNS P2 protein when given nasally before immunization of Lewis rats with bovine PNS myelin (BPM) + Freund's complete adjuvant (FCA). P2 peptide-tolerized rats were also resistant to EAN relapse after challenge with BPM. Tolerance to EAN in rats receiving high dose (60 microg/day/rat) P2 peptide nasally was associated with specific T and B cell anergy. This was characterized by the failure of T cells to proliferate in response to PNS myelin antigens, while responsiveness to phytohemagglutinin was retained. Numbers of BPM- and P2 peptide-reactive interferon-gamma mRNA expressing lymph node cells were reduced, while levels of P2 peptide-reactive interleukin 4 and transforming growth factor-beta mRNA-expressing cells were markedly upregulated on day 18 post immunization in the rats receiving high dose P2 peptide nasally. Tolerance to EAN was also associated with lower CD4+ cell infiltration, low-grade inflammation, or the absence of histological evidence of EAN, as well as with low IL-2 receptor and MHC class II molecule expression within the PNS. This is the first study showing that mucosal tolerance is applicable to EAN and, as an extension, could be considered in GBS.
实验性自身免疫性神经炎（EAN）是一种由CD4 + T细胞介导的外周神经系统（PNS）炎性脱髓鞘疾病，可作为人类格林-巴利综合征（GBS）的模型。EAN和GBS均与T和B细胞对包括P2蛋白在内的PNS髓磷脂蛋白反应上调以及Th1/Th2细胞平衡向Th1倾斜的变化有关。在此我们报告，在用牛PNS髓磷脂（BPM）+弗氏完全佐剂（FCA）免疫Lewis大鼠之前经鼻给予PNS P2蛋白的主要致神经炎肽57 - 81可预防EAN。用P2肽诱导耐受的大鼠在用BPM攻击后对EAN复发也具有抗性。经鼻接受高剂量（60μg/天/只大鼠）P2肽的大鼠对EAN的耐受与特异性T和B细胞无反应性有关。其特征在于T细胞对PNS髓磷脂抗原无增殖反应，而对植物血凝素的反应性得以保留。在经鼻接受高剂量P2肽的大鼠免疫后第18天，表达BPM和P2肽反应性干扰素-γ mRNA的淋巴结细胞数量减少，而表达P2肽反应性白细胞介素4和转化生长因子-β mRNA的细胞水平显著上调。对EAN的耐受还与较低的CD4 +细胞浸润、轻度炎症或缺乏EAN的组织学证据以及PNS内低水平的IL - 2受体和MHC II类分子表达有关。这是第一项表明黏膜耐受适用于EAN的研究，并且作为一种扩展，GBS也可考虑采用黏膜耐受。
