Ohashi P S, Wallace V A, Broughton H, Ohashi C T, Ferrick D A, Jost V, Mak T W, Hengartner H, Pircher H
Department of Experimental Pathology, University Hospital, Zürich, Switzerland.
Eur J Immunol. 1990 Mar;20(3):517-22. doi: 10.1002/eji.1830200309.
A deletion event in the T cell receptor (TcR) delta locus has been characterized in a panel of mouse alpha/beta cytotoxic T lymphocyte (CTL) clones. Data presented here shows that J delta 1, J delta 2 and C delta are absent from functional CTL clones while a germ-line D delta 1 fragment is retained, thus suggesting a specific deletion of this region. We have investigated the possible significance of the J-C delta deletion by generating T cell lines from TcR alpha/beta transgenic mice. Unlike control T cell lines which included a T cell line derived from a beta transgenic mouse, the lines expressing the transgenic alpha/beta heterodimer have not deleted the C delta region. This strongly suggests that the J-C delta deletion event is not responsible for directing T cells to the alpha/beta lineage, but rather is involved in the rearrangement or transcriptional activity of the alpha locus. In addition, to ensure that the alpha/beta transgene does not have any inhibitory affects on the rearrangement of the delta loci in general, the gamma/delta expressing dendritic epithelial T cell (DETC) population was examined in TcR alpha/beta transgenic mice and alterations in this T cell subset were not found. This finding that normal gamma/delta DETC cells are present in alpha/beta transgenic mice, together with the data showing that the D delta 1 region remains in an unrearranged germ-line configuration in functional alpha/beta CTL, suggests that commitment to the alpha/beta or gamma/delta lineage is predetermined at a particular stage in early T cell ontogeny.
在一组小鼠α/β细胞毒性T淋巴细胞(CTL)克隆中,对T细胞受体(TcR)δ基因座的缺失事件进行了表征。此处呈现的数据表明,功能性CTL克隆中不存在Jδ1、Jδ2和Cδ,而保留了种系Dδ1片段,因此表明该区域存在特异性缺失。我们通过从TcRα/β转基因小鼠生成T细胞系,研究了J-Cδ缺失的可能意义。与包括源自β转基因小鼠的T细胞系在内的对照T细胞系不同,表达转基因α/β异二聚体的细胞系并未缺失Cδ区域。这强烈表明,J-Cδ缺失事件并非负责将T细胞导向α/β谱系,而是参与了α基因座的重排或转录活性。此外,为确保α/β转基因总体上对δ基因座的重排没有任何抑制作用,在TcRα/β转基因小鼠中检查了表达γ/δ的树突状上皮T细胞(DETC)群体,未发现该T细胞亚群有改变。在α/β转基因小鼠中存在正常γ/δ DETC细胞这一发现,以及表明Dδ1区域在功能性α/β CTL中保持未重排种系构型的数据,表明在早期T细胞个体发育的特定阶段,对α/β或γ/δ谱系的定向是预先确定的。