Lineage relationships and developmental kinetics of immature thymocytes: CD3, CD4, and CD8 acquisition in vivo and in vitro.
Lineage relationships and developmental kinetics of immature thymocytes: CD3, CD4, and CD8 acquisition in vivo and in vitro.
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DOI：
10.1084/jem.172.6.1583
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发表时间：
1990-12-01
期刊：
影响因子：
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通讯作者：
Shortman K
中科院分区：
文献类型：
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作者：
Petrie HT;Hugo P;Scollay R;Shortman K
T淋巴细胞在胸腺中由免疫幼稚的骨髓前体发育而来。基于T细胞受体的重排和转录，以及胸腺重构的潜力，我们推断了未成熟胸腺细胞在获得谱系标记CD3、CD4和CD8之前的发育序列。在目前的研究中，我们使用两种不同的系统跟踪了该序列中后期的个体发生进展：(a)在体内，通过直接注射到未照射的同源受体胸腺中；(b)体外，使用不含有丝分裂原或细胞因子的培养基。在体内，不太成熟的Pgp-1-白细胞介素2受体α阳性（IL- 2R α +） CD3-4-8-亚群（也是热稳定抗原高）需要3天才能成为主要的IL-2R α - CD3lo4+ 8+典型皮质型细胞，至少5天才能出现任何成熟的单阳性细胞（CD3hi4+ 8-或CD3hi4-8+）。然而，这些Pgp-1- IL-2R α +前体在未刺激的培养中不会进一步分化。更成熟的Pgp-1- IL-2R α - CD3-4-8-亚群在移植后1天内主要变成CD3lo4+ 8+，并且在第3天出现一些成熟的单阳性后代。到第5天，大多数Pgp-1-IL- 2R α -前体细胞变成CD3hi，并且失去或下调CD4或CD8。在培养中，这些ppg -1- IL-2R α -细胞也在1天内获得高水平的CD4和CD8，在2天内获得低水平的CD3。然而，它们在体外不能进一步发展到成熟的单阳性，并且大多数在第3天死亡。这些实验直接证实了我们之前提出的发育序列，并证明了T淋巴细胞在低应激、稳态环境下产生的动力学。
T lymphocytes develop in the thymus from immunologically naive bone marrow precursors. Based on T cell receptor rearrangement and transcription, and thymic reconstitution potential, we have deduced a developmental sequence among immature thymocytes, before the acquisition of the lineage markers CD3, CD4, and CD8. In the current study, we have followed the ontogenic progression of the latter stages in this sequence, using two different systems: (a) in vivo, by direct injection into the thymus of nonirradiated, congenic recipients; and (b) in vitro, using culture medium without mitogens or cytokines. In vivo, the less mature Pgp-1- interleukin 2 receptor alpha-positive (IL- 2R alpha+) CD3-4-8- subset (also heat-stable antigen high) requires 3 d before becoming predominantly IL-2R alpha- CD3lo4+ 8+ typical cortical- type cells, and at least 5 d before the appearance of any mature single- positive cells (CD3hi4+ 8- or CD3hi4-8+). However, these Pgp-1- IL-2R alpha+ precursors do not differentiate further in unstimulated culture. The more mature Pgp-1- IL-2R alpha- CD3-4-8- subset becomes primarily CD3lo4+ 8+ within 1 d after transplantation, and some mature single- positive progeny are evident by day 3. By 5 d, most of these Pgp-1-IL- 2R alpha- precursor cells have become CD3hi, and have lost or are downregulating either CD4 or CD8. In culture, these Pgp-1- IL-2R alpha- cells also acquire high levels of CD4 and CD8 within 1 d, and low levels of CD3 by 2 d. However, they do not progress further to mature single positives in vitro, and most of them die by day 3. These experiments directly confirm our previously proposed developmental sequence, and demonstrate the kinetics of T lymphocyte production in a low-stress, steady-state environment.