Extensive proliferation of T cell lineage-restricted progenitors in the thymus:: an essential process for clonal expression of diverse T cell receptor β chains
Extensive proliferation of T cell lineage-restricted progenitors in the thymus:: an essential process for clonal expression of diverse T cell receptor β chains
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DOI：
10.1002/eji.200323461
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发表时间：
2003-03-01
影响因子：
5.4
通讯作者：
Katsura, Y
中科院分区：
文献类型：
--
作者：
Kawamoto, H;Ohmura, K;Katsura, Y
对于TCR的克隆多样化，需要大量T细胞祖细胞，其中高度多样化的TCRP链被单独容纳。在本研究中，我们研究了胸腺祖细胞的增殖潜力，已被定义为T细胞谱系限制。我们发现，当在胸腺器官培养系统中单独培养时，来自Rag 2（-/-）小鼠的最早的胎儿胸腺（FT）细胞产生150- 1，800个CD 25（+）细胞。由于Rag 2（-/-）胸腺细胞的分化和增殖在TCRP链基因重排阶段被阻止，因此认为观察到的增殖代表TCRP重排前祖细胞的增殖潜力。通过分析正常小鼠FT最早群体中单个祖细胞产生的T细胞的D β-J β重排谱，发现发生了相当水平的增殖。随着发育阶段的进展，前体细胞的增殖能力沿着下降。在限制于T细胞谱系后，祖细胞的这种广泛增殖可能是确保TCR β链克隆多样化的必要过程。
For clonal diversification of TCR, a large number of T cell progenitors are required in which highly diverse TCRP chains are accommodated individually. In the present study, we examined the proliferative potential of thymic progenitors that have been defined to be T cell lineage restricted. We show that the earliest fetal thymus (FT) cells from Rag2(-/-) mice, when cultured individually in a thymic organ culture system, produced 150-1,800 CD25(+) cells. Since differentiation and proliferation of Rag2(-/-) thymocytes are arrested at the stage of TCRP chain gene rearrangement, the observed proliferation was considered to represent the proliferative potential of progenitors prior to the TCRP rearrangement. A comparable level of proliferation was revealed to occur by analyzing the Dbeta-Jbeta rearrangement profiles of T cells generated from single progenitors in the earliest population of FT from normal mice. The proliferative potential of progenitors declined along with the progression of developmental stages. Such an extensive proliferation of progenitors after the restriction to the T cell lineage may be an essential process ensuring the clonal diversification of TCRbeta chains.