The nature of activatory and tolerogenic dendritic cell-derived signal II.
The nature of activatory and tolerogenic dendritic cell-derived signal II.
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DOI：
10.3389/fimmu.2013.00053
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发表时间：
2013
影响因子：
7.3
通讯作者：
de Vries IJ
中科院分区：
文献类型：
--
作者：
Bakdash G;Sittig SP;van Dijk T;Figdor CG;de Vries IJ
树突状细胞 (DC) 通过协调适应性免疫反应，在维持免疫和耐受之间复杂的平衡方面发挥着核心作用。作为最有效的抗原呈递细胞，DC 能够将初始 T 细胞培养为多种效应细胞，从免疫原性 CD4+ T 辅助细胞和细胞毒性 CD8+ T 细胞到耐受性调节性 T 细胞。这种教育基于三个基本信号。信号 I 由与抗原特异性 T 细胞受体结合的抗原/主要组织相容性复合物介导，保证了抗原特异性。由 B7 家族分子介导的共刺激信号 II 对于抗原特异性 T 细胞的扩增至关重要。最后一步是通过信号 III 进行 T 细胞极化，该信号由 DC 衍生的细胞因子传递并决定新兴 T 细胞的效应功能。尽管共刺激被广泛认为是 T 细胞衍生的 CD28 与 DC 表达的 B7 分子 (CD80/CD86) 结合的结果，但其他共刺激途径也已被发现。根据这些途径对引发的 T 细胞的影响，可以将其分为两组。向 T 细胞传递激活信号的途径称为共刺激途径，而向 T 细胞传递耐受原信号的途径称为共抑制途径。在这篇综述中，我们讨论了 DC 衍生信号 II 的性质如何决定随后的 T 细胞反应的质量并最终促进免疫或耐受。彻底了解这一过程有助于确定免疫/耐受平衡扭曲疾病的潜在机制，并有助于创新此类疾病的新治疗方法。
Dendritic cells (DCs) are central in maintaining the intricate balance between immunity and tolerance by orchestrating adaptive immune responses. Being the most potent antigen presenting cells, DCs are capable of educating naïve T cells into a wide variety of effector cells ranging from immunogenic CD4+ T helper cells and cytotoxic CD8+ T cells to tolerogenic regulatory T cells. This education is based on three fundamental signals. Signal I, which is mediated by antigen/major histocompatibility complexes binding to antigen-specific T cell receptors, guarantees antigen specificity. The co-stimulatory signal II, mediated by B7 family molecules, is crucial for the expansion of the antigen-specific T cells. The final step is T cell polarization by signal III, which is conveyed by DC-derived cytokines and determines the effector functions of the emerging T cell. Although co-stimulation is widely recognized to result from the engagement of T cell-derived CD28 with DC-expressed B7 molecules (CD80/CD86), other co-stimulatory pathways have been identified. These pathways can be divided into two groups based on their impact on primed T cells. Whereas pathways delivering activatory signals to T cells are termed co-stimulatory pathways, pathways delivering tolerogenic signals to T cells are termed co-inhibitory pathways. In this review, we discuss how the nature of DC-derived signal II determines the quality of ensuing T cell responses and eventually promoting either immunity or tolerance. A thorough understanding of this process is instrumental in determining the underlying mechanism of disorders demonstrating distorted immunity/tolerance balance, and would help innovating new therapeutic approaches for such disorders.