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首页> 外文期刊>Journal of Neuroimmunology: Official Bulletin of the Research Committee on Neuroimmunology of the World Federation of Neurology >P0 glycoprotein peptides 56-71 and 180-199 dose-dependently induce acute and chronic experimental autoimmune neuritis in Lewis rats associated with epitope spreading.
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P0 glycoprotein peptides 56-71 and 180-199 dose-dependently induce acute and chronic experimental autoimmune neuritis in Lewis rats associated with epitope spreading.

机译:P0糖蛋白肽56-71和180-199剂量依赖性诱导与表位扩散相关的Lewis大鼠急性和慢性实验性自身免疫性神经炎。

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摘要

Two synthetic peripheral nerve myelin P0 protein peptides, an immunodominant (amino acids 180-199) and a cryptic (amino acids 56-71) one, induced an acute or chronic course of experimental autoimmune neuritis (EAN) in Lewis rats, when given at low dose (50-100 microg/rat) or high dose (250 microg/rat), respectively. Corresponding to the different clinical course, pathological changes and immune responses were found: (1) Onset of clinical signs of P0 peptide 56-71 (P0 56-71) induced EAN was 1-3 days later than in P0 peptide 180-199 (P0 180-199) induced EAN at all immunizing doses, whereas the peak of the disease occurred at a similar time point post immunization (p.i.), i.e. at days 14-16 p.i. in P0 56-71 induced EAN and at day 16 p.i. in P0 180-199 induced EAN. (2) Intramolecular epitope spreading as assessed by delayed type hypersensitivity response occurred in P0 56-71 induced EAN at both low and high antigen doses and in P0 180-199 induced EAN at high antigen dose (250 microg/rat) only. (3) P0 180-199 stimulated higher levels of interferon-gamma production in P0 180-199 induced EAN than in P0 56-71 induced EAN and vice versa. (4) Histopathologic evaluation revealed a similar grade of mononuclear cell infiltration in the sciatic nerves of both types of EAN, but more severe demyelination was found in P0 180-199 induced EAN compared to P0 56-71 induced EAN. The results support the hypothesis that high dose autoantigen immunization induces extensive determinant spreading and chronic course of autoimmune diseases.
机译:两种合成的外周神经髓磷脂P0蛋白肽,一种免疫显性(氨基酸180-199)和一种隐秘(氨基酸56-71),在Lewis大鼠中诱导急性或慢性过程性实验性自身免疫性神经炎(EAN)。低剂量(50-100微克/大鼠)或高剂量(250微克/大鼠)。对应于不同的临床病程,发现了病理变化和免疫应答:(1)P0肽56-71(P0 56-71)诱导的EAN的临床体征比P0肽180-199的发病要晚1-3天( P0 180-199)在所有免疫剂量下均可诱发EAN,而疾病的高峰发生在免疫后(pi)的相似时间点,即pi 14-16天在P0 56-71中诱导的EAN和p.i第16天。在P0 180-199中诱发EAN。 (2)仅在高和低剂量的抗原下,P0 56-71诱导的EAN和高抗原剂量(250 microg /大鼠)的P0 180-199诱导的EAN中发生的延迟型超敏反应评估的分子内表位扩散。 (3)在P0 180-199诱发的EAN中,P0 180-199刺激的干扰素-γ产生的水平高于P0 56-71诱发的EAN,反之亦然。 (4)组织病理学评估显示两种类型的EAN的坐骨神经中单核细胞浸润的程度相似,但是与P0 56-71诱导的EAN相比,P0 180-199诱导的EAN发现更严重的脱髓鞘。该结果支持以下假设:高剂量自身抗原免疫可引起广泛的决定因素传播和自身免疫疾病的慢性病程。

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