Abnormal T cell selection on nod thymic epithelium is sufficient to induce autoimmune manifestations in C57BL/6 athymic nude mice.
Abnormal T cell selection on nod thymic epithelium is sufficient to induce autoimmune manifestations in C57BL/6 athymic nude mice.
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DOI：
10.1073/pnas.94.9.4598
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发表时间：
1997-04
影响因子：
11.1
通讯作者：
V. Thomas-Vaslin;D. Damotte;M. Coltey;N. L. Le Douarin;A. Coutinho;J. Salaün
中科院分区：
文献类型：
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作者：
V. Thomas-Vaslin;D. Damotte;M. Coltey;N. L. Le Douarin;A. Coutinho;J. Salaün
为了探讨初级T细胞选择在自身免疫性疾病免疫发病机制中的作用，将非肥胖糖尿病(NOD)胚胎的胸腺上皮(TE)移植到非自身免疫倾向的新生C57BL/6裸鼠体内。结果表明，NOTE选择宿主T细胞库，在其他非糖尿病动物中建立自身免疫。因此，这些嵌合体通常表现为CD4和CD8T细胞介导的岛炎和涎腺炎，与非自身免疫株的TE产生的同基因或异基因嵌合体形成对比。这是首次证明，仅通过改变T细胞选择所涉及的胸腺环境，就可以建立对胰腺β细胞和唾液腺的自身免疫，而不考虑靶器官上主要组织相容性复合体和组织特异性抗原的性质和呈现。这些数据表明，在正常宿主的情况下，NOD胸腺上皮对T细胞的选择足以诱导特定的自身免疫特征。
To investigate the role of primary T cell repertoire selection in the immunopathogenesis of autoimmune diseases, pure thymic epithelium (TE) from nonobese diabetic (NOD) embryos was grafted into non autoimmune prone newborn C57BL/6 athymic mice. The results show that NOD TE selects host T cell repertoires that establish autoimmunity in otherwise nondiabetic animals. Thus, such chimeras regularly show CD4 and CD8 T cell-mediated insulitis and sialitis, in contrast with syngeneic or allogeneic chimeras produced with TE from nonautoimmune strains. This is the first demonstration that autoimmunity to pancreatic beta cells and salivary glands can be established by the sole alteration of the thymic environment involved in T cell selection, regardless of the nature and presentation of both major histocompatibility complex and tissue-specific antigens on the target organ. These data indicate that T cell repertoire selection by the NOD thymic epithelium is sufficient to induce specific autoimmune characteristics in the context of an otherwise normal host.