Petrie H T, Hugo P, Scollay R, Shortman K
Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.
J Exp Med. 1990 Dec 1;172(6):1583-8. doi: 10.1084/jem.172.6.1583.
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.
T淋巴细胞在胸腺中由免疫幼稚的骨髓前体细胞发育而来。基于T细胞受体重排和转录以及胸腺重建潜能，我们推导了未成熟胸腺细胞在获得谱系标志物CD3、CD4和CD8之前的发育序列。在当前研究中，我们使用两种不同的系统追踪了该序列后期阶段的个体发育进程：(a) 在体内，通过直接注射到未受辐射的同基因受体的胸腺中；(b) 在体外，使用不含促有丝分裂原或细胞因子的培养基。在体内，较不成熟的Pgp-1 - 白细胞介素2受体α阳性（IL-2Rα+）CD3-4-8-亚群（也是热稳定抗原高表达）在成为主要的IL-2Rα- CD3lo4+ 8+典型皮质型细胞之前需要3天，在出现任何成熟单阳性细胞（CD3hi4+ 8-或CD3hi4-8+）之前至少需要5天。然而，这些Pgp-1 - IL-2Rα+前体细胞在未刺激的培养中不会进一步分化。较成熟的Pgp-1 - IL-2Rα- CD3-4-8-亚群在移植后1天内主要变为CD3lo4+ 8+，到第3天一些成熟单阳性后代明显可见。到第5天，这些Pgp-1-IL-2Rα-前体细胞中的大多数已变为CD3hi，并已丢失或下调CD4或CD8。在培养中，这些Pgp-1 - IL-2Rα-细胞在1天内也获得高水平的CD4和CD8，到第2天获得低水平的CD3。然而，它们在体外不会进一步发育为成熟单阳性细胞，并且它们中的大多数在第3天死亡。这些实验直接证实了我们先前提出的发育序列，并证明了在低应激、稳态环境中T淋巴细胞产生的动力学。
