MacKenzie-Graham A J, Pribyl T M, Kim S, Porter V R, Campagnoni A T, Voskuhl R R
Reed Neurological Research Center, UCLA Department of Neurology, Los Angeles, CA 90095, USA.
J Immunol. 1997 Nov 1;159(9):4602-10.
Myelin proteins had been thought to be sequestered behind the blood-brain barrier. Recently, however, myelin proteins have been found to be expressed in lymphoid tissues. The myelin basic protein (MBP) gene is embedded within a larger transcription unit called the golli-MBP gene. This larger gene encodes both the "classic" MBPs as well as the structurally related golli-MBPs. In this study, golli-MBP expression in lymph nodes was examined in four different models of relapsing experimental autoimmune encephalomyelitis (rEAE). Disease in these rEAE models was induced by the adoptive transfer of T lymphocytes specific for 18.5-kDa MBP, MBP peptide 83-102, or PLP peptide 139-151 in the SJL/J mouse and the adoptive transfer of T lymphocytes specific for MBP peptide Ac1-9 in the (SJL/J x PL/J)F1 mouse. In all four models, expression of golli-MBP BG21 mRNA was increased two- to fivefold in lymph nodes of mice 45 to 60 days post-transfer. Immunohistochemical analysis indicated that expression occurred principally in macrophages within lymph nodes. Endogenous golli-MBP epitopes within lymph node cells stimulated "classic" MBP 1-44-specific T lymphocytes, and this stimulatory ability resided within the adherent lymph node cell population. An increase in myelin protein expression within lymph nodes during rEAE has implications with regard to intra- and intermolecular epitope spreading. This is the first report describing an increase in target autoantigen expression within lymphoid tissue during an autoimmune disease.
髓磷脂蛋白一直被认为被隔离在血脑屏障之后。然而，最近发现髓磷脂蛋白在淋巴组织中表达。髓磷脂碱性蛋白（MBP）基因嵌入在一个名为golli-MBP基因的更大转录单元中。这个更大的基因既编码“经典”MBP，也编码结构相关的golli-MBP。在本研究中，在四种不同的复发性实验性自身免疫性脑脊髓炎（rEAE）模型中检测了淋巴结中golli-MBP的表达。这些rEAE模型中的疾病是通过在SJL/J小鼠中过继转移针对18.5-kDa MBP、MBP肽83-102或PLP肽139-151的T淋巴细胞，以及在（SJL/J×PL/J）F1小鼠中过继转移针对MBP肽Ac1-9的T淋巴细胞诱导的。在所有四种模型中，转移后45至60天的小鼠淋巴结中golli-MBP BG21 mRNA的表达增加了2至5倍。免疫组织化学分析表明，表达主要发生在淋巴结内的巨噬细胞中。淋巴结细胞内的内源性golli-MBP表位刺激了“经典”MBP 1-44特异性T淋巴细胞，这种刺激能力存在于贴壁淋巴结细胞群体中。rEAE期间淋巴结内髓磷脂蛋白表达的增加与分子内和分子间表位扩展有关。这是第一份描述自身免疫性疾病期间淋巴组织中靶自身抗原表达增加的报告。
