Adams T E
Department of Veterinary Preclinical Sciences, University of Melbourne, Parkville, Victoria, Australia.
Mol Biol Med. 1990 Aug;7(4):341-57.
Transgenic mice represent a versatile experimental approach for understanding the pathways by which the immune system regulates responsiveness to self-antigens, thereby establishing self-tolerance. The introduction of immunoglobulin and T cell receptor genes with specificity for self-antigens into the germline of mice has enabled the fate of self-reactive lymphocyte precursors to be followed in vivo. The influence of both developmentally regulated, and tissue-specific gene expression on tolerance to self-antigens has been addressed using transgenic mice expressing novel self-antigens under the transcriptional control of heterologous gene promoters. The generation of transgenic mice expressing structurally altered forms of self-antigens has allowed the role of antigen-processing in the induction of tolerance to be examined. Significantly, while these studies have confirmed the classically derived principles of immunological self-tolerance, they also point to the existence of pathways, as yet undefined, by which tolerance to self-antigens may be implemented and maintained.
转基因小鼠是一种通用的实验方法，用于理解免疫系统调节对自身抗原反应性从而建立自身耐受性的途径。将对自身抗原有特异性的免疫球蛋白和T细胞受体基因导入小鼠种系，使得体内能够追踪自身反应性淋巴细胞前体的命运。利用在异源基因启动子转录控制下表达新型自身抗原的转基因小鼠，研究了发育调控和组织特异性基因表达对自身抗原耐受性的影响。表达结构改变形式自身抗原的转基因小鼠的产生，使得能够研究抗原加工在耐受性诱导中的作用。重要的是，虽然这些研究证实了经典推导的免疫自身耐受性原则，但它们也指出存在尚未明确的途径，通过这些途径可以实现和维持对自身抗原的耐受性。
