Pircher H, Ohashi P, Miescher G, Lang R, Zikopoulos A, Bürki K, Mak T W, MacDonald H R, Hengartner H
Department of Experimental Pathology, University Hospital, Zürich, Switzerland.
Eur J Immunol. 1990 Feb;20(2):417-24. doi: 10.1002/eji.1830200227.
To study allelic exclusion of TcR genes we analyzed two types (I and II) of TcR beta transgenic mice. T cells derived from both types of mice contained similar amounts of transgenic RNA transcripts; however, surface expression of the transgenic beta chain was drastically reduced in type II compared to type I. In type I transgenic mice, productive rearrangements and expression of endogenous TcR beta genes were suppressed whereas on T cells of type II mice, both transgenic and endogenous TcR beta chains were expressed on the surface of the same cell. These findings suggest that allelic exclusion of TcR genes in beta transgenic mice depends on amount and/or onset of transgene expression during thymic development. Furthermore, TcR gamma rearrangements and the population of TcR gamma/delta-bearing double-negative CD4-CD8- thymocytes were reduced fivefold in type I transgenic animals. However, the V gamma usage and the gamma/delta+ dendritic epidermal cell populations appeared normal. RNase protection analysis further revealed low levels of transgenic TcR beta chain transcripts in TcR+ gamma/delta CD4-CD8- thymocytes. These results suggest that the beta transgene only quantitatively influences the gamma/delta T cell compartment, and supports the independence of the gamma/delta population.
为了研究T细胞受体（TcR）基因的等位基因排斥，我们分析了两种类型（I型和II型）的TcRβ转基因小鼠。来自这两种小鼠的T细胞含有相似数量的转基因RNA转录本；然而，与I型相比，II型小鼠中转基因β链的表面表达显著降低。在I型转基因小鼠中，内源性TcRβ基因的有效重排和表达受到抑制，而在II型小鼠的T细胞上，转基因和内源性TcRβ链在同一细胞表面表达。这些发现表明，β转基因小鼠中TcR基因的等位基因排斥取决于胸腺发育过程中转基因表达的量和/或起始时间。此外，在I型转基因动物中，TcRγ重排以及携带TcRγ/δ的双阴性CD4-CD8-胸腺细胞群体减少了五倍。然而，Vγ的使用情况以及γ/δ+树突状表皮细胞群体看起来正常。核糖核酸酶保护分析进一步揭示，在TcR+γ/δ CD4-CD8-胸腺细胞中，转基因TcRβ链转录本水平较低。这些结果表明，β转基因仅在数量上影响γ/δ T细胞区室，并支持γ/δ群体的独立性。
