Salmon P, Boyer O, Lorès P, Jami J, Klatzmann D
Laboratory of Biology and Therapeutics of Immunity Pathology, Pitié-Salpêtrière Hospital, Paris, France.
J Immunol. 1996 Mar 1;156(5):1873-9.
The expression of the CD4 gene undergoes a complex pattern of regulation during T cell development. Results obtained in transgenic mice suggest that a combination of proximal enhancer and a silencer from the CD4 gene is sufficient to obtain a developmentally controlled expression along T cell maturation. We generated transgenic mice expressing the human CD4 cDNA under the control of the human CD4 promoter and the murine CD4 minimal proximal enhancer. No other regulatory sequences, including the silencer, were included. The pattern of expression of this transgene is restricted to mature peripheral T cells, to the only mature heat-stable Ag(HSA)low/- single positive thymocytes, and to some NK cells. Surprisingly, no expression was found in double positive or in immature HSAhigh single positive thymocytes. These results suggest that additional, yet uncharacterized genomic sequences are necessary for CD4 expression in immature thymocytes and that there is a change in transcription factors occurring at the late states of T cell development. Finally, since this is the first combination of regulatory sequences that possess such a T mature specific pattern of expression, it should provide a novel tool to address several immunologic questions or for therapeutic purposes.
CD4基因的表达在T细胞发育过程中经历复杂的调控模式。在转基因小鼠中获得的结果表明，CD4基因近端增强子和沉默子的组合足以在T细胞成熟过程中实现发育调控的表达。我们构建了在人CD4启动子和小鼠CD4最小近端增强子控制下表达人CD4 cDNA的转基因小鼠。未包含其他调控序列，包括沉默子。该转基因的表达模式仅限于成熟外周T细胞、仅成熟的热稳定抗原（HSA）低/ -单阳性胸腺细胞以及一些NK细胞。令人惊讶的是，在双阳性或未成熟的HSA高单阳性胸腺细胞中未发现表达。这些结果表明，未成熟胸腺细胞中CD4表达需要其他尚未鉴定的基因组序列，并且在T细胞发育后期转录因子发生了变化。最后，由于这是具有这种T成熟特异性表达模式的调控序列的首次组合，它应为解决几个免疫学问题或用于治疗目的提供一种新工具。
