van Dongen J J, Wolvers-Tettero I L, Wassenaar F, Borst J, van den Elsen P
Department of Immunology, University Hospital Dijkzigt/Erasmus University, Rotterdam, The Netherlands.
Blood. 1989 Jul;74(1):334-42.
We have analyzed T-cell receptor delta (TcR-delta) gene rearrangement and transcription in appropriately phenotyped mononuclear cells derived from 12 patients with T-cell acute lymphoblastic leukemia (T-ALL). The T-ALL cells were also analyzed for rearrangement and transcription of the T-cell receptor(TcR)-beta and gamma genes as well as for the presence of TcR-alpha gene transcripts. Four T-ALLs expressed TcR-gamma delta at the cell surface, while three expressed TcR-alpha beta. The other five T-ALLs did not express a TcR-CD3 complex on their cell membrane. The TcR-gamma delta + T-ALL had rearranged both TcR-delta gene alleles and contained mature 2.2 and 1.5 kb TcR-delta transcripts. In one case, immature 1.9 and 1.2 kb TcR-delta transcripts were also found. Furthermore they contained mature TcR-gamma mRNA, mature or immature TcR-beta mRNA, but no TcR-alpha mRNA. The three TcR-alpha beta + T-ALLs contained mature alpha and beta transcripts, but lacked TcR-delta transcripts as a result of deletion of both TcR-delta gene alleles. These data are in line with a mutually exclusive expression of TcR-alpha and -delta genes, which may be important to ensure the presence of only one type of TcR per T cell. One of the five CD3- T-ALLs had germline TcR-beta, gamma, and delta genes. The other four CD3- T-ALLs had rearranged their TcR-beta, gamma, and delta genes and contained immature 1.9 and 1.2 kb TcR-delta gene transcripts. Remarkably, one of these T-ALLs also contained TcR-alpha transcripts in addition to the immature TcR-delta transcripts, which was in line with the deletion of one TcR-delta gene allele and rearrangement of the other allele. This suggests that prevention of dual receptor expression may not only be regulated by the presence of germline TcR-alpha genes in TcR-gamma delta + cells or by deletion of both TcR-delta gene alleles in TcR-alpha beta + cells, but also via other regulation mechanisms. Finally, our data indicated that the combinatorial repertoire of the TcR-delta genes is limited, which has also been described for the TcR-gamma genes.
我们分析了12例T细胞急性淋巴细胞白血病（T-ALL）患者来源的经适当表型鉴定的单核细胞中的T细胞受体δ（TcR-δ）基因重排和转录情况。同时也对T-ALL细胞进行了T细胞受体（TcR）-β和γ基因的重排及转录分析，以及TcR-α基因转录本的检测。4例T-ALL细胞表面表达TcR-γδ，3例表达TcR-αβ。另外5例T-ALL细胞膜上未表达TcR-CD3复合物。TcR-γδ⁺ T-ALL的两个TcR-δ基因等位基因均发生重排，并含有成熟的2.2 kb和1.5 kb TcR-δ转录本。在1例中，还发现了未成熟的1.9 kb和1.2 kb TcR-δ转录本。此外，它们还含有成熟的TcR-γ mRNA、成熟或未成熟的TcR-β mRNA，但没有TcR-α mRNA。3例TcR-αβ⁺ T-ALL含有成熟的α和β转录本，但由于两个TcR-δ基因等位基因均缺失，缺乏TcR-δ转录本。这些数据与TcR-α和-δ基因的相互排斥性表达一致，这对于确保每个T细胞仅存在一种类型的TcR可能很重要。5例CD3⁻ T-ALL中的1例具有种系TcR-β、γ和δ基因。另外4例CD3⁻ T-ALL的TcR-β、γ和δ基因发生了重排，并含有未成熟的1.9 kb和1.2 kb TcR-δ基因转录本。值得注意的是，其中1例T-ALL除了未成熟的TcR-δ转录本外，还含有TcR-α转录本，这与一个TcR-δ基因等位基因缺失和另一个等位基因重排一致。这表明防止双受体表达可能不仅受TcR-γδ⁺细胞中种系TcR-α基因的存在或TcR-αβ⁺细胞中两个TcR-δ基因等位基因缺失的调节，还受其他调节机制的影响。最后，我们的数据表明TcR-δ基因的组合库是有限的，这在TcR-γ基因中也曾有描述。
