Institute for Immunology, Hannover Medical School, Hannover, Germany.
Blood. 2010 Feb 11;115(6):1137-44. doi: 10.1182/blood-2009-07-230821. Epub 2009 Dec 15.
T-cell development in the thymus depends on continuous supply of T-cell progenitors from bone marrow (BM). Several extrathymic candidate progenitors have been described that range from multipotent cells to lymphoid cell committed progenitors and even largely T-lineage committed precursors. However, the nature of precursors seeding the thymus under physiologic conditions has remained largely elusive and it is not known whether there is only one physiologic T-cell precursor population or many. Here, we used a competitive in vivo assay based on depletion rather than enrichment of classes of BM-derived precursor populations, thereby only minimally altering physiologic precursor ratios to assess the contribution of various extrathymic precursors to T-lineage differentiation. We found that under these conditions multiple precursors, belonging to both multipotent progenitor (MPP) and common lymphoid progenitor (CLP) subsets have robust T-lineage potential. However, differentiation kinetics of different precursors varied considerably, which might ensure continuous thymic output despite gated importation of extrathymic precursors. In conclusion, our data suggest that the thymus functions to impose T-cell fate on any precursor capable of filling the limited number of progenitor niches.
胸腺中的 T 细胞发育依赖于骨髓（BM）中不断供应 T 细胞祖细胞。已经描述了几种胸腺外候选祖细胞，范围从多能细胞到淋巴样细胞定向祖细胞，甚至是高度 T 系定向前体。然而，在生理条件下播种胸腺的前体的性质在很大程度上仍然难以捉摸，并且不知道是否只有一个生理 T 细胞前体群体或多个。在这里，我们使用了一种基于耗竭而不是 BM 衍生前体群体的富集的竞争体内测定法，从而仅最小程度地改变生理前体比来评估各种胸腺外前体对 T 系分化的贡献。我们发现，在这些条件下，属于多能祖细胞（MPP）和共同淋巴样祖细胞（CLP）亚群的多个前体具有强大的 T 系潜力。然而，不同前体的分化动力学差异很大，这可能确保尽管有胸腺外前体的门控导入，但仍能持续产生胸腺输出。总之，我们的数据表明，胸腺的功能是将 T 细胞命运强加于任何有能力填补有限数量的祖细胞龛的前体上。
