Sustained CD28 expression delays multiple features of replicative senescence in human CD8 T lymphocytes.
Sustained CD28 expression delays multiple features of replicative senescence in human CD8 T lymphocytes.
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DOI：
10.1007/s10875-010-9449-7
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发表时间：
2010-11
影响因子：
9.1
通讯作者：
Effros, Rita B.
中科院分区：
文献类型：
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作者：
Parish, Stanley T.;Wu, Jennifer E.;Effros, Rita B.
T淋巴细胞中的CD 28共刺激信号转导对于最佳端粒酶活性、细胞因子mRNA的稳定和葡萄糖代谢是必不可少的。在衰老和HIV-1慢性感染期间，缺乏CD 28表达的CD 8 T淋巴细胞比例增加，并显示出复制性衰老的其他特征。此外，这些细胞的丰度与疫苗反应性降低、老年人的早期死亡率和加速艾滋病毒疾病进展有关。在这里，我们表明，CD 28的持续表达，通过基因转导，延缓复制衰老的过程中，证明了增强端粒酶活性，增加整体增殖潜力，并减少促炎细胞因子的分泌。然而，转导的培养物最终确实达到衰老，这与CTLA-4基因表达增加和CD 28细胞表面表达丧失相关。这些发现进一步阐明了CD 28在复制性衰老过程中的核心作用，并可能最终导致与复制性衰老相关的疾病的新疗法。
CD28 costimulatory signal transduction in T lymphocytes is essential for optimal telomerase activity, stabilization of cytokine mRNAs, and glucose metabolism. During aging and chronic infection with HIV-1, there are increased proportions of CD8 T lymphocytes that lack CD28 expression and show additional features of replicative senescence. Moreover, the abundance of these cells correlates with decreased vaccine responsiveness, early mortality in the very old, and accelerated HIV disease progression. Here, we show that sustained expression of CD28, via gene transduction, retards the process of replicative senescence, as evidenced by enhanced telomerase activity, increased overall proliferative potential, and reduced secretion of pro-inflammatory cytokines. Nevertheless, the transduced cultures eventually do reach senescence, which is associated with increased CTLA-4 gene expression and a loss of CD28 cell surface expression. These findings further elucidate the central role of CD28 in the replicative senescence program, and may ultimately lead to novel therapies for diseases associated with replicative senescence.
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影响因子：
8.7
作者：
Rudd CE;Taylor A;Schneider H
通讯作者：
Schneider H
影响因子：
3.9
作者：
Appay, Victor;Almeida, Jorge R.;Papagno, Laura
通讯作者：
Papagno, Laura
影响因子：
3.9
作者：
PERILLO, NL;WALFORD, RL;EFFROS, RB
通讯作者：
EFFROS, RB
影响因子：
56.9
作者：
FRASER, JD;IRVING, BA;WEISS, A
通讯作者：
WEISS, A
DOI：
10.4049/jimmunol.0903647
发表时间：
2010-03-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Parish ST;Kim S;Sekhon RK;Wu JE;Kawakatsu Y;Effros RB
通讯作者：
Effros RB