Intrathymic expression of genes involved in organ specific autoimmune disease
Intrathymic expression of genes involved in organ specific autoimmune disease
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DOI：
10.1006/jaut.1998.0210
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发表时间：
1998-08-01
影响因子：
12.8
通讯作者：
Mason, DW
中科院分区：
文献类型：
--
作者：
Heath, VL;Moore, NC;Mason, DW
胰岛素、甲状腺球蛋白和髓鞘碱性蛋白（MBP）作为自身抗原参与自身免疫性疾病、胰岛素依赖型糖尿病（IDDM）、自身免疫性甲状腺疾病和多发性硬化症。对这些抗原的自我耐受性，直到最近才被认为存在于胸腺外，通常被认为是通过“外周”机制维持的，如克隆能量或克隆无知。利用逆转录和聚合酶链反应（RT-PCR）技术研究这些基因在胸腺内的表达。研究了从完整成年大鼠胸腺、从胎儿胸腺器官培养物中分离的各种小鼠胸腺细胞类型和从新生小鼠胸腺细胞亚群中分离的mRNA的表达。在未分离的成年大鼠和胚胎小鼠胸腺中检测胰岛素、甲状腺球蛋白和MBP的mRNA表达。大鼠胸腺同时表达胰岛素I和胰岛素II，而小鼠胸腺只表达胰岛素II。在小鼠MHCⅱ类+胸腺上皮细胞和ⅱ类+树突状细胞以及某些胸腺细胞亚群中检测到甲状腺球蛋白和MBP，但未检测到胰岛素mRNA。胸腺中胰岛素、甲状腺球蛋白和MBP mRNA的存在对t细胞库的发展具有重要意义，特别是对健康个体中阻止这些抗原自身反应的耐受性机制具有重要意义。(C) 1998学术出版社。
Insulin, thyroglobulin and myelin basic protein (MBP) are implicated as autoantigens in the autoimmune diseases, insulin-dependent diabetes mellitus (IDDM), autoimmune thyroid-disease and multiple sclerosis. Self tolerance to these antigens, until recently only thought to be present extrathymically, is generally considered to be maintained by 'peripheral' mechanisms, such as clonal anergy or clonal ignorance. The techniques of reverse transcription and polymerase chain reaction (RT-PCR) were used to investigate the intrathymic expression of these genes. Expression was examined in mRNA isolated from complete adult rat thymus, various mouse thymic cell-types isolated from fetal thymic-organ cultures and from neonatal-mouse thymocyte subsets. mRNA for insulin, thyroglobulin and MBP were detected in unfractionated adult rat and embryonic mouse thymus. Rat thymus expressed both insulin I and II, while mouse thymus only expressed insulin II. Thyroglobulin and MBP, but not insulin mRNA were detected in mouse MHC class II+ thymic epthelial cells and class II+ dendritic cells and in certain thymocyte subsets. The presence of insulin, thyroglobubin and MBP mRNA in the thymus has important implications for the development of the T-cell repertoire, particularly for the mechanisms of tolerance that prevent autoreactivity to these antigens in healthy individuals. (C) 1998 Academic Press.