Godfrey D I, Kennedy J, Mombaerts P, Tonegawa S, Zlotnik A
DNAX Research Institute, Palo Alto, CA 94304.
J Immunol. 1994 May 15;152(10):4783-92.
TCR-beta gene rearrangement or expression is necessary and sufficient for the progression of early alpha beta thymocyte differentiation from the CD3-CD4-CD8- triple negative (TN)3 to the CD4+CD8+ double positive stage. The onset of TCR-beta rearrangement is currently thought to occur gradually. Some thymocytes were reported to be rearranged at the earliest (CD44+CD25-) TN stage, whereas other thymocytes did not initiate TCR-beta rearrangement until the latest (CD44-CD25-) TN stage. Here, we have isolated subsets of TN thymocytes on the basis of surface expression of CD44 and CD25, with c-kit as an additional marker. We present a revised model of early T cell development in which TCR-beta and TCR-gamma rearrangements occur abruptly, at the CD44lowCD25+ c-kitlowTN stage. A high level of c-kit expression defines pro-T cells which have not yet rearranged their TCR genes. Germ-line TCR-beta transcripts, and transcripts of recombination activating genes (RAG)-1 and 2, are detected before TCR-beta gene rearrangement. Analyses of TN thymocytes of RAG-1 mutant mice, and of various TCR mutant and TCR transgenic RAG-1 mutant mice, indicate the existence of a control point at the CD44-CD25+TN stage at which cells expressing a productively rearranged TCR-beta chain are selected for further differentiation.
TCR-β基因重排或表达对于早期αβ胸腺细胞从CD3-CD4-CD8-三阴性（TN）3阶段向CD4+CD8+双阳性阶段的分化进程而言是必要且充分的。目前认为TCR-β重排的起始是逐渐发生的。据报道，一些胸腺细胞最早在（CD44+CD25-）TN阶段就发生了重排，而其他胸腺细胞直到最晚的（CD44-CD25-）TN阶段才开始TCR-β重排。在此，我们基于CD44和CD25的表面表达，并将c-kit作为一个额外的标志物，分离出了TN胸腺细胞亚群。我们提出了一个早期T细胞发育的修正模型，其中TCR-β和TCR-γ重排是在CD44lowCD25+c-kitlowTN阶段突然发生的。高水平的c-kit表达定义了尚未重排其TCR基因的前T细胞。在TCR-β基因重排之前可检测到种系TCR-β转录本以及重组激活基因（RAG）-1和2的转录本。对RAG-1突变小鼠的TN胸腺细胞以及各种TCR突变和TCR转基因RAG-1突变小鼠的分析表明，在CD44-CD25+TN阶段存在一个控制点，在该控制点，表达有效重排的TCR-β链的细胞会被选择进行进一步分化。
