Jolicoeur C, Hanahan D, Smith K M
Department of Biochemistry and Biophysics, University of California, San Francisco 94143-0534.
Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6707-11. doi: 10.1073/pnas.91.14.6707.
Transgenic mice expressing T antigen (Tag) in pancreatic beta cells establish systemic tolerance toward this self-protein. The self-tolerance in two families of rat insulin promoter (RIP)-Tag mice, expressing different levels of Tag protein, has been characterized. These mice have impaired antibody responses to Tag, show diminished Tag-specific T-cell proliferation, and evidence an inability to generate Tag-specific cytotoxic T cells. The existence of systemic tolerance toward a beta-cell-specific protein motivated examination of transgene expression in the thymus. Indeed, low levels of Tag mRNA were detected intrathymically. Remarkably, this expression is a valid property of the insulin gene regulatory region, since insulin RNA was also expressed in the thymus of nontransgenic mice. RNA for other pancreatic genes was also detected in the thymus, thus raising the possibility that many tissue-specific genes could be expressed intrathymically during immunological development and induction of self-tolerance. These results raise important questions for future research into the role of the thymus in tolerance induction toward so-called tissue-specific antigens.
在胰腺β细胞中表达T抗原（Tag）的转基因小鼠对这种自身蛋白建立了全身耐受性。已对两个表达不同水平Tag蛋白的大鼠胰岛素启动子（RIP）-Tag小鼠家族的自身耐受性进行了表征。这些小鼠对Tag的抗体反应受损，Tag特异性T细胞增殖减少，并且证明无法产生Tag特异性细胞毒性T细胞。对β细胞特异性蛋白的全身耐受性的存在促使人们对胸腺中的转基因表达进行研究。确实，在胸腺内检测到了低水平的Tag mRNA。值得注意的是，这种表达是胰岛素基因调控区的一个有效特性，因为在非转基因小鼠的胸腺中也表达了胰岛素RNA。在胸腺中还检测到了其他胰腺基因的RNA，因此增加了许多组织特异性基因在免疫发育和自身耐受性诱导过程中可能在胸腺内表达的可能性。这些结果为未来研究胸腺在对所谓组织特异性抗原的耐受性诱导中的作用提出了重要问题。
