4-1BBL costimulation retrieves CD28 expression in activated T cells
4-1BBL costimulation retrieves CD28 expression in activated T cells
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DOI：
10.1016/j.cellimm.2009.01.003
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发表时间：
2009-01-01
影响因子：
4.3
通讯作者：
Searle, Peter F.
中科院分区：
文献类型：
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作者：
Habib-Agahi, Mojtaba;Jaberipour, Mansooreh;Searle, Peter F.
CD80/86 与 CD28 的结合被认为是主要的 T 细胞共刺激相互作用。然而，T 细胞激活后不久，CD28 就会下调。为了研究 CD137 (4-IBB) 和 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 T 细胞，并使用重组非复制腺病毒转导到细胞中。初始T细胞增殖后，CD4(+)和CD8(+)群体中CD28(+)细胞的比例因CD80/86共刺激而迅速减少，而仅用4-1BBL共刺激的培养物继续表达CD28。 CD28 在 CD80/86 和 4-1BBL 共刺激的培养物中也下调。有趣的是，在用 CD80/86 共刺激的细胞中，CD28 表达下调并停止增殖，通过 4-1BBL 共刺激重新激活增殖也恢复了其 CD28 表达。这些发现表明 CD137 信号传导对 CD28 表达具有积极影响，类似于 T 细胞激活初始阶段 CD28 参与对 4-1BB 表达的影响。此外，他们还指出了通过 4-1BB 的信号对于离体 T 细胞激活和扩增的重要性。 (C) 2009 Elsevier Inc. 保留所有权利。
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-IBB) 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. (C) 2009 Elsevier Inc. All rights reserved.