Immortalization of human CD8+ T cell clones by ectopic expression of telomerase reverse transcriptase

Immortalization of human CD8+ T cell clones by ectopic expression of telomerase reverse transcriptase
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DOI:
10.4049/jimmunol.165.8.4239
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发表时间:
2000-10-15
影响因子:
4.4
通讯作者:
Spits, H
Spits, H
中科院分区:
医学2区
文献类型:
--
作者:
Hooijberg, E;Ruizendaal, JJ;Spits, H

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T细胞的复制性衰老与端粒末端的侵蚀有关。端粒酶在维持端粒长度方面起着关键作用。因此,端粒酶被认为调节T细胞的寿命。为了验证这一假设,我们在人CD8(+)T细胞中过表达人端粒酶逆转录酶。人端粒酶逆转录酶的异位表达导致这些T细胞的永生化,而不改变表型,也不丧失特异性或功能性。由于T细胞在体外扩增仍然依赖于细胞因子和Ag刺激,因此我们得出结论,在没有恶性转化的情况下实现了永生化。
Replicative senescence of T cells is correlated with erosion of telomere ends. Telomerase plays a key role in maintaining telomere length. Therefore, it is thought that telomerase regulates the life span of T cells. To test this hypothesis, we have over-expressed human telomerase reverse transcriptase in human CD8(+) T cells. Ectopic expression of human telomerase reverse transcriptase led to immortalization of these T cells, without altering the phenotype and without loss of specificity or functionality. As the T cells remained dependent on cytokines and Ag stimulation for their in vitro expansion, we conclude that immortalization was achieved without malignant transformation.