Paillard F, Sterkers G, Vaquero C
Laboratoire d'Immunologie et Oncologie des Maladies Rétrovirales, INSERM U 152, CNRS URA 628, Hôpital Cochin, Paris, France.
EMBO J. 1990 Jun;9(6):1867-72. doi: 10.1002/j.1460-2075.1990.tb08312.x.
We previously showed that the turnover rates of the messengers coding for the T cell receptor (TcR) alpha, beta and gamma, CD4 and CD8 molecules composing the multireceptor complex vary in normal human mature T lymphocytes according to their state of activation. Activation by soluble anti-CD3 which does not induce proliferation, promotes a weak up-modulation of the corresponding five mRNAs. In contrast, activation signals such as anti-CD3 + PMA, which lead to lymphokine mRNA expression and T cell proliferation, promote a decrease of the TcR, CD4 and CD8 mRNA levels within 4 h post-activation, followed by their gradual re-expression. Here we show that the down-modulation of these mRNAs results from early regulation controls at transcriptional and post-transcriptional levels, i.e. through a concomitant inhibition of transcription and destabilization of the mRNA. Moreover, later re-expression of the mRNA results from recovery of transcription and marked increase of the mRNA stability. Finally, down-modulation is specific for TcR, CD4 and CD8 mRNAs, all submitted to similar regulation processes. These results strongly suggest a direct correlation between down-modulation of the multireceptor complex mRNAs, and lymphokine mRNA expression, and cellular proliferation.
我们先前表明，编码T细胞受体（TcR）α、β和γ、构成多受体复合物的CD4和CD8分子的信使RNA的周转率，在正常人类成熟T淋巴细胞中根据其激活状态而有所不同。由不诱导增殖的可溶性抗CD3激活，会促进相应五种mRNA的微弱上调。相反，诸如抗CD3 + PMA等激活信号，会导致淋巴因子mRNA表达和T细胞增殖，在激活后4小时内促进TcR、CD4和CD8 mRNA水平的下降，随后它们会逐渐重新表达。在这里我们表明，这些mRNA的下调是由转录和转录后水平的早期调控控制所致，即通过转录的同时抑制和mRNA的去稳定化。此外，mRNA的后期重新表达是由于转录的恢复和mRNA稳定性的显著增加。最后，下调对TcR、CD4和CD8 mRNA具有特异性，它们都受到相似的调控过程。这些结果有力地表明，多受体复合物mRNA的下调与淋巴因子mRNA表达和细胞增殖之间存在直接关联。
