Chemokine-mediated control of T cell traffic in lymphoid and peripheral tissues
Chemokine-mediated control of T cell traffic in lymphoid and peripheral tissues
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DOI：
10.1016/j.molimm.2004.06.040
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发表时间：
2005-05-01
影响因子：
3.6
通讯作者：
Moser, B
中科院分区：
文献类型：
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作者：
Ebert, LA;Schaerli, P;Moser, B
抗原驱动的T细胞驯化以及随后病原体的清除对免疫系统提出了特殊挑战。病原体通常在周边部位进入身体，比如皮肤、胃肠道或肺部，这些部位基本上没有初始T细胞。相反，初始T细胞不断在次级淋巴器官（如淋巴结和派尔集合淋巴结）中循环，以寻找通过输入淋巴管被带到这些位置的抗原。在这里，负载抗原的树突状细胞将抗原 - 肽 - MHC复合物呈递给克隆型T细胞，并为免疫反应的启动提供适当的共刺激信号。结果，产生了短寿命的效应T细胞和长寿命的记忆T细胞，它们到达外周组织参与免疫反应和免疫监视。效应T细胞和记忆T细胞的迁移不是随机的，这是由于组织特异性的“地址编码”使其能够正确归巢到组织。这个过程涉及黏附分子，包括选择素、整合素以及相应的血管配体，还有趋化因子大家族及其受体。在此，我们讨论T细胞激活和分化过程中趋化因子受体表达的变化，以及这些变化对初始、效应和记忆T细胞迁移潜能的影响。我们总结了目前对T细胞归巢到次级淋巴组织内T区和B细胞滤泡的理解，并强调两种趋化因子受体CCR7和CXCR5，它们分别识别在T区（CCR7配体CCL19/ELC和CCL21/SLC）或滤泡区（CXCR5配体CXCL13/BCA - 1）组成性存在的趋化因子。CCR7是初始T细胞和中枢记忆T（T - CM）细胞的特征，而CXCR5可区分滤泡辅助性B细胞T（T - FH）细胞。此外，我们进一步将长寿命记忆T细胞细分为CCR7阴性的效应记忆T（T - EM）细胞和外周免疫监视T（T - PS）细胞。后一个术语指的是主要驻留在正常（健康）外周组织中的非常大的记忆T细胞亚群。我们目前对T - PS细胞迁移和功能的理解非常零碎，但这些细胞被认为在病原体进入部位提供局部即时保护。在此，我们提出T - PS细胞的组织分布是由一组独特的趋化因子和相应受体决定的，这与在次级淋巴组织和炎症部位起作用的趋化因子和受体不同。（c）2004爱思唯尔有限公司。保留所有权利。
Antigen-driven T cell education and subsequent pathogen elimination present particular challenges for the immune system. Pathogens generally enter the body at peripheral sites such as the skin, gastrointestinal tract or lung, areas from which naive T cells are largely excluded. Instead, naive T cells constantly recirculate through secondary lymphoid organs, such as lymph nodes and Peyer's patches, in search for antigen brought to these locations by means of afferent lymphatic channels. Here, antigen-loaded dendritic cells present antigen-peptide-MHC complexes to clonotypic T cells and provide appropriate co-stimulatory signals for immune response initiation. As a result, short-lived effector T cells and long-lived memory T cells are generated that reach the peripheral tissue for participation in immune responses and immune surveillance.Effector and memory T cell relocation is non-random, due to tissue-specific "address codes" that allow proper tissue homing. This process involves adhesion molecules, including selectins, integrins, and corresponding vascular ligands as well as the large family of chemokines and their receptors. Here, we discuss the changes in chemokine receptor expression that occur during T cell activation and differentiation, and the ways in which these changes impact on the migration potential of naive, effector, and memory T cells. We summarize our current understanding of T cell homing to the T zone and B cell follicles within secondary lymphoid tissues and highlight the two chemokine receptors CCR7 and CXCR5 that recognize chemokines constitutively present either in the T zone (CCR7 ligands CCL19/ELC and CCL21/SLC) or follicular compartment (CXCR5 ligand CXCL13/BCA-1). CCR7 is characteristic for naive and central memory T (T-CM) cells whereas CXCR5 distinguishes follicular B helper T (T-FH) cells. In addition, we further subdivide long-lived memory T cells into CCR7-negative effector memory T (T-EM) cells and peripheral immune surveillance T (T-PS) cells. The latter term designates the extraordinarily large subset of memory T cells with primary residence in normal (healthy) peripheral tissues. Our current understanding of T-PS cell migration and function is highly fragmentary, but these cells are thought to provide immediate protection locally at the site of pathogen entry. Here, we propose that the tissue distribution of T-PS cells is determined by a distinct set of chemokines and corresponding receptors that differs from those operating in secondary lymphoid tissues and inflammatory sites. (c) 2004 Elsevier Ltd. All rights reserved.