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首页> 外文期刊>Cellular immunology >4-1BBL costimulation retrieves CD28 expression in activated T cells.
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4-1BBL costimulation retrieves CD28 expression in activated T cells.

机译:4-1BBL共刺激可在活化的T细胞中检索CD28表达。

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摘要

Binding of CD80/86 to CD28 is regarded as the main T cell costimulatory interaction. However, CD28 downregulates soon after T cell activation. To investigate potential cross-interaction between CD137 (4-1BB) and CD28, we stimulated T cells with anti-CD3 in the presence of A549 lung carcinoma cells expressing CD80/CD86 and 4-1BBL molecules, transduced into the cells using recombinant non-replicating adenoviruses. Following initial T cell proliferation, the proportion of CD28(+) cells in both CD4(+) and CD8(+) populations was rapidly reduced by CD80/86 costimulation, whereas cultures costimulated with just 4-1BBL continued to express CD28. CD28 was also downregulated in cultures costimulated with both CD80/86 and 4-1BBL. Interestingly, in cells costimulated with CD80/86 that had downregulated CD28 expression and ceased to proliferate, reactivation of proliferation by 4-1BBL costimulation also restored their CD28 expression. These findings show a positive effect of CD137 signalling on CD28 expression, similar to the effect of CD28 engagement on 4-1BB expression during the initial phases of T cell activation. Moreover, they point to the importance of signals through 4-1BB for the purposes of ex-vivo T cell activation and expansion.
机译:CD80 / 86与CD28的结合被认为是主要的T细胞共刺激相互作用。但是,CD28在T细胞活化后立即下调。为研究CD137(4-1BB)与CD28之间潜在的交叉相互作用,我们在表达CD80 / CD86和4-1BBL分子的A549肺癌细胞存在下,用抗CD3刺激了T细胞。复制腺病毒。最初的T细胞增殖后,CD80 / 86共刺激迅速降低了CD4(+)和CD8(+)群体中CD28(+)细胞的比例,而仅用4-1BBL共刺激的培养物继续表达CD28。在与CD80 / 86和4-1BBL共同刺激的培养物中,CD28也被下调。有趣的是,在用CD80 / 86共刺激的细胞中,CD28 / 86的表达下调并停止增殖,通过4-1BBL共刺激的增殖激活也恢复了其CD28的表达。这些发现显示了CD137信号传导对CD28表达的积极影响,类似于在T细胞活化的初始阶段CD28参与对4-1BB表达的影响。此外,他们指出通过4-1BB进行信号对于活体T细胞活化和扩增的重要性。

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