Garcia-Sanz J A, Lenig D
Basel Institute for Immunology, Switzerland.
J Exp Med. 1996 Jul 1;184(1):159-64. doi: 10.1084/jem.184.1.159.
T cell stimulation by triggering through the T cell receptor (TCR) in the absence of costimulatory signals or by calcium ionophore induces unresponsiveness in T cells to further stimulation, a phenomenon known as anergy. In freshly isolated T cells, calcium ionophore induces expression of interleukin (IL)-2 messenger (mRNA), but this mRNA is not translated and not loaded with ribosomes. In addition, while plate-bound anti-CD3 stimulation of resting T cells leads to IL-2 mRNA expression and IL-2 secretion, in cells pretreated with calcium ionophore before anti-CD3 stimulation, the IL-2 mRNA remains polysome unloaded and no IL-2 is produced. These observations show that IL-2 expression is controlled at the translational level, by differential ribosome loading. Furthermore, our data suggest that translational control of IL-2 mRNA may be a molecular mechanism by which anergy is attained.
在没有共刺激信号的情况下,通过T细胞受体(TCR)触发或使用钙离子载体刺激T细胞,会导致T细胞对进一步刺激无反应,这种现象称为无反应性。在新鲜分离的T细胞中,钙离子载体可诱导白细胞介素(IL)-2信使核糖核酸(mRNA)的表达,但这种mRNA不会被翻译,也不会与核糖体结合。此外,虽然平板结合的抗CD3刺激静止T细胞会导致IL-2 mRNA表达和IL-2分泌,但在抗CD3刺激前用钙离子载体预处理的细胞中,IL-2 mRNA仍未与多核糖体结合,也不会产生IL-2。这些观察结果表明,IL-2的表达在翻译水平上受到核糖体加载差异的控制。此外,我们的数据表明,IL-2 mRNA的翻译控制可能是实现无反应性的分子机制。