Mehr R, Segel L, Sharp A, Globerson A
Department of Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
J Theor Biol. 1994 Oct 7;170(3):247-57. doi: 10.1006/jtbi.1994.1185.
The early events of T-cell generation, i.e. seeding of bone marrow-derived progenitor cells onto the thymic stroma, involve a small fraction (up to 1%) of thymus cells and are not presently observable. However, these events are crucial in determining the outcome of thymic colonization. In previous studies we utilized an experimental in vitro model of thymic reconstitution by bone marrow cells to compare normal thymocyte development with the development in conditions of T-cell deficiency, and, in particular, in aging. These studies showed that progenitor cells from old donor bone marrow are deficient in their ability to colonize the thymus, in spite of their ability to divide earlier upon seeding. In this study we apply mathematical and computer modelling in order to analyse early T-cell development and the causes for the developmental disadvantage of old donor bone marrow cells. The results indicate that the competition for seeding niches in the thymic stroma determines the outcome of colonization.
T细胞生成的早期事件，即骨髓来源的祖细胞在胸腺基质上的定植，涉及一小部分（高达1%）胸腺细胞，目前无法观察到。然而，这些事件对于决定胸腺定植的结果至关重要。在先前的研究中，我们利用骨髓细胞进行胸腺重建的体外实验模型，比较正常胸腺细胞发育与T细胞缺陷条件下，特别是衰老条件下的发育情况。这些研究表明，来自老年供体骨髓的祖细胞尽管在接种后早期具有分裂能力，但其在胸腺定植的能力存在缺陷。在本研究中，我们应用数学和计算机建模来分析早期T细胞发育以及老年供体骨髓细胞发育劣势的原因。结果表明，胸腺基质中定植微环境的竞争决定了定植的结果。
