The effect of in vivo IL-7 deprivation on T cell maturation.
The effect of in vivo IL-7 deprivation on T cell maturation.
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DOI：
10.1084/jem.181.4.1399
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发表时间：
1995-04-01
期刊：
影响因子：
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通讯作者：
Waldschmidt TJ
中科院分区：
文献类型：
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作者：
Bhatia SK;Tygrett LT;Grabstein KH;Waldschmidt TJ
先前的许多研究表明白细胞介素 7 (IL-7) 在 T 淋巴细胞的成熟中发挥着关键作用。为了更好地评估 IL-7 在淋巴细胞生成中的功能，我们通过长期施用中和性抗 IL-7 抗体来剥夺小鼠体内的 IL-7。在之前的报告中（Grabstein、K. H.、T. J. Waldschmidt、F. D. Finkelman、B. W. Hess、A. R. Alpert、N. E. Boiani、A. E. Namen 和 P. J. Morrissey. 1993. J. Exp. Med. 178:257-264），我们使用该系统证明了 IL-7 在 B 细胞成熟中的关键作用。经过短暂的抗 IL-7 治疗后，骨髓中的大多数原 B 细胞以及所有前 B 细胞和未成熟 B 细胞都被耗尽。在本报告中，我们注射了抗 IL-7 抗体长达 12 周，以确定体内 IL-7 剥夺对胸腺的影响。结果表明，长期施用抗体后，胸腺细胞结构减少了 > 99%。对胸腺 CD4- 和 CD8- 定义的亚群的检查显示，按比例计算，CD4+、CD8+ 亚群最为匮乏，CD4 和 CD8 单阳性细胞基本保持不变，而 CD4-、CD8- 区室实际上增加到胸腺的约 50%。对双阴性胸腺细胞的进一步检查表明，IL-7 剥夺确实耗尽了 CD3-、CD4-、CD8- 前体细胞，并且该亚群的扩张在 CD44+、CD25+ 阶段被中断。发现 CD4-、CD8- 区室的成比例增加是由于 CD3+、T 细胞受体 α、β + 双阴性 T 细胞的积累。额外的分析表明，抗 IL-7 治疗抑制了 T 细胞的试听/选择过程，如表达 CD69 和热稳定抗原的单个阳性细胞显着减少所示。最后，发现IL-7剥夺对胸腺的影响是可逆的，胸腺亚群在停止治疗后4周恢复正常模式。因此，目前的结果表明 IL-7 在胸腺来源的 T 细胞的成熟中起着核心作用。
A number of previous studies have suggested a key role for interleukin 7 (IL-7) in the maturation of T lymphocytes. To better assess the function of IL-7 in lymphopoiesis, we have deprived mice of IL-7 in vivo by long-term administration of a neutralizing anti-IL-7 antibody. In a previous report (Grabstein, K. H., T. J. Waldschmidt, F. D. Finkelman, B. W. Hess, A. R. Alpert, N. E. Boiani, A. E. Namen, and P. J. Morrissey. 1993. J. Exp. Med. 178:257-264), we used this system to demonstrate the critical role of IL-7 in B cell maturation. After a brief period of anti-IL-7 treatment, most of the pro-B cells and all of the pre-B and immature B cells were depleted from the bone marrow. In the present report, we have injected anti-IL-7 antibody for periods of up to 12 wk to determine the effect of in vivo IL-7 deprivation on the thymus. The results demonstrate a > 99% reduction in thymic cellularity after extended periods of antibody administration. Examination of thymic CD4- and CD8- defined subsets revealed that, on a proportional basis, the CD4+, CD8+ subset was most depleted, the CD4 and CD8 single positive cells remained essentially unchanged, and the CD4-, CD8- compartment actually increased to approximately 50% of the thymus. Further examination of the double negative thymocytes demonstrated that IL-7 deprivation did, indeed, deplete the CD3-, CD4-, CD8- precursors, with expansion of this subset being interupted at the CD44+, CD25+ stage. The proportional increase in the CD4-, CD8- compartment was found to be due to an accumulation of CD3+, T cell receptor alpha, beta + double negative T cells. Additional analysis revealed that anti-IL-7 treatment suppressed the audition/selection process of T cells, as shown by a significant reduction of single positive cells expressing CD69 and heat stable antigen. Finally, the effects of IL-7 deprivation on the thymus were found to be reversible, with a normal pattern of thymic subsets returning 4 wk after cessation of treatment. The present results thus indicate a central role for IL-7 in the maturation of thymic-derived T cells.