Influence of activating stimulus on functional phenotype: interleukin 2 mRNA accumulation differentially induced by ionophore and receptor ligands in subsets of murine T cells.

Influence of activating stimulus on functional phenotype: interleukin 2 mRNA accumulation differentially induced by ionophore and receptor ligands in subsets of murine T cells.
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激活刺激对功能表型的影响:小鼠 T 细胞亚群中离子载体和受体配体差异诱导的白细胞介素 2 mRNA 积累。

DOI:
10.1073/pnas.85.17.6503
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发表时间:
1988
影响因子:
11.1
通讯作者:
Rothenberg,EV
Rothenberg,EV
中科院分区:
综合性期刊1区
文献类型:
--
作者:
McGuire,KL;Yang,JA;Rothenberg,EV

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我们已经研究了CD 4/CD 8表型和原代T细胞群体中特异性应答的编程之间的联系。原位杂交已被用来确定频率的细胞有能力表达白细胞介素2(IL-2)基因的短期刺激后,与各种多克隆激活剂。T细胞受体配体Con A和抗CD 3单克隆抗体的效果进行了比较与钙离子载体,完全绕过膜受体。用钙离子载体和佛波醇酯诱导显示,潜在的IL-2产生者不仅构成了具有CD 4+“辅助/诱导”表型的细胞的85%以上,而且构成了具有CD 8+“杀伤/抑制”表型的细胞的一半以上。在这些条件下,这些CD 8+细胞积累IL-2转录物的能力没有缺陷。相比之下,响应佛波酯和Con A或抗CD 3,CD 8+细胞显示IL-2产生应答失败,IL-2 mRNA快速消失。这导致每个细胞的IL-2产量显著低于响应相同刺激的CD 4+细胞的产量。因此,这些群体在功能上出现分歧的程度取决于用于触发反应的刺激。结果表明,信号转导或转录后调控机制的差异,而不是效应基因诱导本身,可能最初的承诺的CD 4+和CD 8+细胞不同的功能作用的基础。
We have investigated the linkage between CD4/CD8 phenotype and programming for specific responses in primary T-cell populations. In situ hybridization has been used to determine the frequency of cells competent to express the interleukin 2 (IL-2) gene after short-term stimulation with various polyclonal activators. The effects of the T-cell receptor ligands Con A and anti-CD3 monoclonal antibody were compared with those of a calcium ionophore that bypasses membrane receptors altogether. Induction with a calcium ionophore and phorbol ester revealed that potential IL-2 producers not only constitute greater than 85% of the cells with a CD4+ "helper/inducer" phenotype but also constitute over half of the cells with a CD8+ "killer/suppressor" phenotype. There is no defect in the ability of these CD8+ cells to accumulate IL-2 transcripts under these conditions. By contrast, in response to phorbol ester and either Con A or anti-CD3, the CD8+ cells show an abortive IL-2 production response with rapid disappearance of IL-2 mRNA. This results in substantially lower yields of IL-2 per cell than is made by CD4+ cells in response to the same stimuli. The extent to which these populations appear to have diverged in function thus depends on the stimulus used to trigger the response. The results suggest that differences in signal transduction or posttranscriptional regulatory mechanisms, rather than effector gene inducibility per se, may initially underlie the commitment of CD4+ and CD8+ cells to distinct functional roles.