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体内未成熟小鼠胸腺细胞发育的动力学

The kinetics of immature murine thymocyte development in vivo.

作者信息

Egerton M, Shortman K, Scollay R

机构信息

Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.

出版信息

Int Immunol. 1990;2(6):501-7. doi: 10.1093/intimm/2.6.501.

DOI:10.1093/intimm/2.6.501
PMID:2128186
Abstract

The dynamics of cell generation and turnover in the young adult murine thymus has been studied by in vivo administration of [6-3H]deoxythymidine, isolation of thymocyte subpopulations by negative depletion and cell sorting procedures, and assessment of dividing cells and their products by autoradiography. The flow of label through subpopulations of CD4-CD8- thymocytes defined by the markers heat stable antigen (HSA), phagocyte glycoprotein 1 (Pgp-1), interleukin 2 receptor (p55) (IL-2R), and CD3 was determined, to check the developmental sequence deduced from intrathymic transfer and molecular approaches. In addition, the flow of label 'downstream' into the CD4+CD8+ cortical populations was followed to check if cells expressing CD8 alone were obligatory intermediates. The main findings were: (i) support for the following sequence within the CD4-CD8- group: HSA++Pgp-1+IL-2R(-)----HSA++Pgp-1-IL-2R(+)----HSA++Pgp-1-IL- 2R-; (ii) the majority of cell generation and cell turnover within the CD4-CD8- population was due to the HSA++IL-2R-Pgp-1- subpopulation; (iii) the rate of cell output from the proposed intermediate CD3-CD4-CD8+ subpopulation was equivalent to only 55% of the cell output from its proposed precursor, the most mature CD4-CD8- subpopulation, suggesting that many double negatives differentiate directly (or via CD3-CD4+CD8- intermediates) into double positives; and (iv) the CD4-CD8-HSA- (and CD3+) thymic subpopulation contained very few cycling cells and turned over extremely slowly, indicating that these slowly accumulating product cells are off the mainstream of T cell development.

摘要

通过体内给予[6-³H]脱氧胸苷、采用阴性去除和细胞分选程序分离胸腺细胞亚群以及通过放射自显影评估分裂细胞及其产物,对年轻成年小鼠胸腺中细胞生成和更替的动力学进行了研究。确定了标记物通过由热稳定抗原(HSA)、吞噬细胞糖蛋白1(Pgp-1)、白细胞介素2受体(p55)(IL-2R)和CD3所定义的CD4⁻CD8⁻胸腺细胞亚群的流动情况,以检验从胸腺内转移和分子方法推导出来的发育顺序。此外,追踪标记物“下游”进入CD4⁺CD8⁺皮质群体的流动情况,以检查仅表达CD8的细胞是否为必需的中间产物。主要发现如下:(i)支持CD4⁻CD8⁻组内的以下顺序:HSA⁺⁺Pgp-1⁺IL-2R⁻----HSA⁺⁺Pgp-1⁻IL-2R⁺----HSA⁺⁺Pgp-1⁻IL-2R⁻;(ii)CD4⁻CD8⁻群体内的大多数细胞生成和细胞更替归因于HSA⁺⁺IL-2R⁻Pgp-1⁻亚群;(iii)从假定的中间CD3⁻CD4⁻CD8⁺亚群输出细胞的速率仅相当于其假定前体(最成熟的CD4⁻CD8⁻亚群)输出细胞速率的55%,这表明许多双阴性细胞直接(或通过CD3⁻CD4⁺CD8⁻中间产物)分化为双阳性细胞;(iv)CD4⁻CD8⁻HSA⁻(和CD3⁺)胸腺亚群包含极少的循环细胞且更替极其缓慢,这表明这些缓慢积累的产物细胞偏离了T细胞发育的主流。

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