Killeen N, Sawada S, Littman D R
Howard Hughes Medical Institute, University of California, San Francisco 94143-0414.
EMBO J. 1993 Apr;12(4):1547-53. doi: 10.1002/j.1460-2075.1993.tb05798.x.
During T cell development, precursor thymocytes that co-express the CD4 and CD8 glycoproteins give rise to mature progeny expressing one of these molecules to the exclusion of the other. Continued expression of only CD4 is the hallmark of mature helper T cells, whereas cytotoxic T cells express CD8 and extinguish CD4. The differentiation program that generates the two T cell subsets is likely to be intimately tied to regulation of expression of these cell surface molecules. We now describe the use of a murine CD4 enhancer in the generation of transgenic mice expressing physiologic levels of human CD4. The transgene is appropriately regulated during T cell development and includes the necessary cis-acting sequences for extinguishing expression in the CD8 lineage. Furthermore, in mice whose endogenous CD4 gene is inactivated, the transgenic human CD4 mediates rescue of the CD4 lineage and restoration of normal helper cell functions. The generation of these mice exemplifies a general approach for developing reliable animal models for the human immune system.
在T细胞发育过程中，共表达CD4和CD8糖蛋白的前体胸腺细胞会产生成熟后代，这些后代只表达其中一种分子而排斥另一种分子。仅持续表达CD4是成熟辅助性T细胞的标志，而细胞毒性T细胞表达CD8并停止表达CD4。产生这两种T细胞亚群的分化程序可能与这些细胞表面分子表达的调节密切相关。我们现在描述了在生成表达生理水平人类CD4的转基因小鼠过程中使用小鼠CD4增强子的情况。该转基因在T细胞发育过程中得到适当调节，并且包含在CD8谱系中停止表达所需的顺式作用序列。此外，在内源性CD4基因失活的小鼠中，转基因人类CD4介导CD4谱系的拯救和正常辅助细胞功能的恢复。这些小鼠的产生例证了一种开发人类免疫系统可靠动物模型的通用方法。
