Xing Zheng, Conway Edward M, Kang Chulho, Winoto Astar
Department of Molecular and Cell Biology, Division of Immunology and Cancer Research Laboratory, University of California at Berkeley, 469 LSA, Berkeley, CA 94720, USA.
J Exp Med. 2004 Jan 5;199(1):69-80. doi: 10.1084/jem.20031588. Epub 2003 Dec 29.
Survivin is an inhibitor of apoptosis protein that also functions during mitosis. It is expressed in all common tumors and tissues with proliferating cells, including thymus. To examine its role in apoptosis and proliferation, we generated two T cell-specific survivin-deficient mouse lines with deletion occurring at different developmental stages. Analysis of early deleting survivin mice showed arrest at the pre-T cell receptor proliferating checkpoint. Loss of survivin at a later stage resulted in normal thymic development, but peripheral T cells were immature and significantly reduced in number. In contrast to in vitro studies, loss of survivin does not lead to increased apoptosis. However, newborn thymocyte homeostatic and mitogen-induced proliferation of survivin-deficient T cells were greatly impaired. These data suggest that survivin is not essential for T cell apoptosis but is crucial for T cell maturation and proliferation, and survivin-mediated homeostatic expansion is an important physiological process of T cell development.
生存素是一种凋亡抑制蛋白，在有丝分裂过程中也发挥作用。它在所有常见肿瘤以及包括胸腺在内的具有增殖细胞的组织中表达。为了研究其在凋亡和增殖中的作用，我们构建了两个T细胞特异性生存素缺陷小鼠品系，缺失发生在不同的发育阶段。对早期缺失生存素的小鼠的分析显示，其在pre-T细胞受体增殖检查点处停滞。在后期阶段生存素缺失导致胸腺发育正常，但外周T细胞不成熟且数量显著减少。与体外研究相反，生存素缺失不会导致凋亡增加。然而，新生胸腺细胞的稳态以及生存素缺陷T细胞的丝裂原诱导增殖受到极大损害。这些数据表明，生存素对于T细胞凋亡并非必不可少，但对于T细胞成熟和增殖至关重要，并且生存素介导的稳态扩增是T细胞发育的一个重要生理过程。
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