An Enigmatic Tail of CD28 Signaling
An Enigmatic Tail of CD28 Signaling
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DOI：
10.1101/cshperspect.a002436
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发表时间：
2010-08-01
影响因子：
7.2
通讯作者：
Green, Jonathan M.
中科院分区：
文献类型：
--
作者：
Boomer, Jonathan S.;Green, Jonathan M.
CD28共刺激调节了广泛的细胞过程，从增殖和存活到促进专用T细胞亚群的分化。自20年前首次被鉴定出来以来，CD28一直是一项激烈研究的主题，因为它对T细胞功能及其治疗操作的潜力产生了深远的影响。在这篇综述中，我们强调了CD28中主要信号基序引发的信号传导级联反应，重点是PI-3激酶依赖性途径和非依赖性途径，以及这些途径如何与特定的细胞结果相关。最近使用基因靶向敲门蛋白小鼠的研究阐明了这些基序对体内免疫反应的相对重要性。但是，还有很多尚待阐明。了解共刺激背后的机制具有开发新的临床相关试剂的巨大潜力，这一事实开始通过阻止CD28结扎和信号传导的药物出现来实现这一事实。
CD28 costimulation regulates a wide range of cellular processes, from proliferation and survival to promoting the differentiation of specialized T-cell subsets. Since first being identified over 20 years ago, CD28 has remained a subject of intense study because of its profound consequences on T cell function and its potential for therapeutic manipulation. In this review we highlight the signaling cascades initiated by the major signaling motifs in CD28, focusing on PI-3 kinase-dependent and -independent pathways and how these are linked to specific cellular outcomes. Recent studies using gene targeted knockin mice have clarified the relative importance of these motifs on in vivo immune responses; however, much remains to be elucidated. Understanding the mechanism behind costimulation holds great potential for development of new clinically relevant reagents, a fact beginning to be realized with the advent of drugs that prevent CD28 ligation and signaling.