CD28 expression is required after T cell priming for helper T cell responses and protective immunity to infection.
CD28 expression is required after T cell priming for helper T cell responses and protective immunity to infection.
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DOI：
10.7554/elife.03180
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发表时间：
2014-10-27
期刊：
影响因子：
7.7
通讯作者：
Smith KG
中科院分区：
文献类型：
--
作者：
Linterman MA;Denton AE;Divekar DP;Zvetkova I;Kane L;Ferreira C;Veldhoen M;Clare S;Dougan G;Espéli M;Smith KG
共刺激分子CD 28对于辅助性T细胞的活化是必需的。尽管有这种关键作用，但尚不清楚CD 28是否具有在活化后维持T细胞应答的功能。为了确定CD 28在T细胞致敏后的作用，我们产生了一种小鼠品系，其中在致敏后从CD 4 + T细胞中除去CD 28。我们表明，持续的CD 28表达是重要的效应CD 4 + T细胞感染后，维持CD 28是所需的辅助性T细胞1型细胞的扩增，并在病毒感染过程中的T滤泡辅助细胞的分化和维护。持久性CD 28也是从胃肠道清除啮齿类柠檬酸杆菌所必需的。总之，这项研究表明，CD 28的持久性是所需的辅助T细胞极化响应感染，描述了一种新的功能，CD 28是不同的作用，在T细胞启动。http://dx.doi.org/10.7554/eLife.03180.001细菌或病毒的入侵通常会激活哺乳动物宿主的免疫系统以消除病原体。所谓的“先天免疫系统”的细胞是身体抵抗感染的第一道防线，这些细胞在器官和组织中巡逻，以迅速定位和消除病原体。先天免疫反应迅速且非特异性，但通常无法完全清除感染。必要时，先天性免疫细胞将通过激活免疫系统的第二个分支（称为“适应性免疫系统”）来增强免疫应答。这是专门针对和根除入侵的病原体。T细胞是适应性免疫系统的重要组成部分，这些细胞可以通过在其表面发现的称为T细胞受体（或TCR）的蛋白质容易地与其他类型的细胞区分开来。也有不同类型的T细胞，每种都有特定的功能。例如，T辅助细胞帮助其他适应性免疫细胞成熟和激活，这涉及这些免疫细胞增殖和发育成更专门的细胞。要激活T细胞，必须同时发生两个事件。首先，TCR必须识别并结合由先天免疫细胞呈递给它的病原体片段。其次，T细胞和同一先天免疫细胞表面的“共刺激分子”必须相互作用。使用这两种信号来激活T细胞有助于确保适应性免疫反应不会不必要地“释放”。共刺激分子已经成为治疗自身免疫性疾病的流行靶点，这种疾病是免疫系统攻击并破坏人体自身组织的疾病。T细胞表达的共刺激分子之一被称为CD 28;然而，CD 28是否参与T细胞活化后的任何过程仍然未知。现在，Linterman等人揭示了除了T细胞活化之外，CD 28共刺激分子还起着许多作用。例如，一个新开发的小鼠模型表明，CD 28必须保留在T辅助细胞的表面上，在它们被激活后，这些细胞才能有效地专门化。Linterman等人还发现，CD 28有助于不同的T辅助细胞亚型的发育。Linterman等人证明，CD 28在宿主对感染的反应中是至关重要的，并表明如果活化的T细胞上的CD 28丢失（这在衰老、HIV感染和自身免疫性疾病期间发生），则T辅助细胞的反应变得有限。此外，这些发现揭示了靶向CD 28共刺激分子的治疗也会影响正在进行的免疫应答。DOI：http://dx.doi.org/10.7554/eLife.03180.002网站
The co-stimulatory molecule CD28 is essential for activation of helper T cells. Despite this critical role, it is not known whether CD28 has functions in maintaining T cell responses following activation. To determine the role for CD28 after T cell priming, we generated a strain of mice where CD28 is removed from CD4+ T cells after priming. We show that continued CD28 expression is important for effector CD4+ T cells following infection; maintained CD28 is required for the expansion of T helper type 1 cells, and for the differentiation and maintenance of T follicular helper cells during viral infection. Persistent CD28 is also required for clearance of the bacterium Citrobacter rodentium from the gastrointestinal tract. Together, this study demonstrates that CD28 persistence is required for helper T cell polarization in response to infection, describing a novel function for CD28 that is distinct from its role in T cell priming. DOI: http://dx.doi.org/10.7554/eLife.03180.001 Invasion by a bacterium or virus typically activates a mammalian host's immune system to eliminate the pathogen. The cells of the so-called ‘innate immune system’ are the body's first line of defense against infection, and these cells patrol the organs and tissues in an effort to locate and eliminate pathogens quickly. The innate immune response is rapid and non-specific, but often cannot completely clear an infection. When necessary, innate immune cells will escalate the immune response by activating the second branch of the immune system, called the ‘adaptive immune system’. This specifically targets and eradicates an invading pathogen. T cells are essential components of the adaptive immune system, and these cells can be readily distinguished from other types of cell by proteins called T cell receptors (or TCRs) found on their surface. There are also different types of T cell, each with a specific function. T helper cells, for example, help other adaptive immune cells to mature and activate, which involves these immune cells proliferating and developing into more specialized cells. For a T cell to activate, two events must occur at the same time. First, the TCR must recognize and bind to a fragment of the pathogen that is presented to it by an innate immune cell. And second, ‘co-stimulatory molecules’ present on the surfaces of both the T cell and the same innate immune cell must interact. Using these two signals to activate a T cell helps to ensure the adaptive immune response is not ‘unleashed‘ unnecessarily. Co-stimulatory molecules have become popular targets for therapies aimed at treating autoimmune disorders—where the immune system attacks and destroys the body's own tissues. One of the most well studied co-stimulatory molecules expressed by T cells is called CD28; however, it remained unknown whether CD28 is involved in any processes after T cell activation. Now, Linterman et al. reveal that the CD28 co-stimulatory molecule plays a number of roles in addition to T cell activation. For example, a newly developed mouse model showed that CD28 must remain on the surface of T helper cells after they have been activated for these cells to effectively specialize. Linterman et al. also discovered that CD28 helps different T helper cell subtypes to develop. Linterman et al. demonstrate that CD28 is critical throughout a host's response to infection, and suggest that if CD28 is lost on activated T cells (which happens during aging, HIV infection and autoimmune diseases) the responses of T helper cells become limited. Furthermore, these findings reveal that treatments that target the CD28 co-stimulatory molecule will also affect on-going immune responses. DOI: http://dx.doi.org/10.7554/eLife.03180.002