An alternative splice variant of human IL-4, IL-4 delta 2, inhibits IL-4-stimulated T cell proliferation.
An alternative splice variant of human IL-4, IL-4 delta 2, inhibits IL-4-stimulated T cell proliferation.
复制标题
人 IL-4 的另一种剪接变体 IL-4 delta 2 可抑制 IL-4 刺激的 T 细胞增殖。
DOI：
10.4049/jimmunol.156.2.435
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发表时间：
1996
影响因子：
4.4
通讯作者：
Barbara White
中科院分区：
文献类型：
--
作者：
S. Atamas;Jung Choi;V. Yurovsky;Barbara White
mRNA 的选择性剪接可以产生蛋白质亚型，这些蛋白质亚型优先在不同组织中或在细胞分化或激活的不同状态下表达。蛋白质亚型可能具有不同的功能。在这项研究中，我们克隆、表达并测试了人类 IL-4 天然存在的剪接变体（称为 IL-4 delta 2）的功能效果。在 IL-4 delta 2 中，IL-4 的第二个外显子通过选择性剪接被省略，外显子 1、3 和 4 连接在开放阅读框中。我们发现 IL-4 delta 2 RNA 在所有测试供体的 PBMC 中表达，通常含量低于 IL-4 RNA。相反，IL-4 δ 2 RNA 在胸腺细胞和支气管肺泡灌洗细胞中的表达水平比 IL-4 RNA 高得多，表明表达的组织特异性。 IL-4 delta 2 cDNA 在酵母中表达。重组人 (rh) IL-4 delta 2 经部分纯化，发现已糖基化，蛋白核心为 13 至 15 kDa。与 rhIL-4 不同，rhIL-4 delta 2 并不充当 T 细胞增殖的共刺激剂。然而，rhIL-4 delta 2 抑制了 rhIL-4 作为 T 细胞共刺激剂的能力。抑制与糖基化无关，并且不受毒性介导。发现碘化 IL-4 delta 2 与已知表达 IL-4 受体的人 PBMC 和肿瘤系特异性结合。过量未标记的 IL-4 会抑制标记的 IL-4 delta 2 的细胞结合。因此，rhIL-4 delta 2 是 IL-4 的天然剪接变体，优先在胸腺和气道中表达，并抑制完整 IL-4 的功能。 IL-4 和 IL-4 delta 2 之间的平衡对于 IL-4 效应的调节可能很重要。
Alternative splicing of mRNA can generate protein isoforms that are preferentially expressed in different tissues or during different states of cell differentiation or activation. Protein isoforms may have different functions. In this study, we cloned, expressed, and tested functional effects of a naturally occurring splice variant of human IL-4, called IL-4 delta 2. In IL-4 delta 2, the second exon of IL-4 is omitted by alternative splicing, with exons 1, 3, and 4 joined in an open reading frame. We found that IL-4 delta 2 RNA is expressed in the PBMC of all donors tested, usually in lower amounts than IL-4 RNA. In contrast, IL-4 delta 2 RNA is expressed in much higher levels than IL-4 RNA in thymocytes and bronchoalveolar lavage cells, suggesting tissue specificity of expression. IL-4 delta 2 cDNA was expressed in yeast. Recombinant human (rh) IL-4 delta 2 was partially purified and found to be glycosylated, with a protein core of 13 to 15 kDa. Unlike rhIL-4, rhIL-4 delta 2 did not act as a costimulator for T cell proliferation. However, rhIL-4 delta 2 inhibited the ability of rhIL-4 to act as a T cell costimulator. Inhibition was independent of glycosylation and was not mediated by toxicity. Iodinated IL-4 delta 2 was found to bind specifically to human PBMC and tumor lines known to express IL-4 receptors. Excess unlabeled IL-4 inhibited cellular binding of labeled IL-4 delta 2. Thus, rhIL-4 delta 2 is a naturally occurring splice variant of IL-4 that is preferentially expressed in the thymus and airways and inhibits function of complete IL-4. The balance between IL-4 and IL-4 delta 2 may be important in the regulation of IL-4 effects.