Impaired accumulation of antigen-specific CD8 lymphocytes in chemokine CCL25-deficient intestinal epithelium and lamina propria
Impaired accumulation of antigen-specific CD8 lymphocytes in chemokine CCL25-deficient intestinal epithelium and lamina propria
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DOI：
10.4049/jimmunol.178.12.7598
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发表时间：
2007-06-15
影响因子：
4.4
通讯作者：
Campbell, James J.
中科院分区：
文献类型：
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作者：
Wurbel, Marc-Andre;Malissen, Marie;Campbell, James J.
CCL25和CCR9构成一对趋化因子/受体，参与T细胞发育和肠道相关免疫反应。在这项研究中，我们产生了CCL25(-/-)小鼠来回答现有CCR9(-/-)小鼠无法回答的问题。在CCL25(-/-)和CCR9(-/-)小鼠中观察到了相似的表型，这与CCL25和CCR9相互作用的概念是一致的。我们评估了CCL25在产生CCR9(高)CD8肠道记忆表型T细胞方面的需求，以及这些细胞随后在效应部位的积累。将转TCR基因的初始CD8T细胞转移到野生型或CCL25缺陷宿主中。用Ag口服致敏使这些幼稚的供体细胞在野生型宿主的肠系膜淋巴结内有效地分化为CCR9(高记忆性)表型细胞。这一分化事件在CCL25缺陷宿主的MLN中以同样的效率发生，表明CCL25不是体内诱导CCR9(高)记忆表型所必需的。然而，我们发现CCL25缺乏严重损害了供体来源的CD8T细胞在小肠固有层和上皮内的Ag依赖聚集。因此，尽管CCL25不是产生具有“肠道归巢”特性的记忆表型CD8 T细胞所必需的，但这种趋化因子对于它们运输到小肠是必不可少的。
CCL25 and CCR9 constitute a chemokine/receptor pair involved in T cell development and in gut-associated immune responses. In this study, we generated CCL25(-/-) mice to answer questions that could not be addressed with existing CCR9(-/-) mice. Similar phenotypes were observed for both CCL25(-/-) and CCR9(-/-) mice, consistent with the notion that CCL25 and CCR9 interact with each other exclusively. We assessed the requirement for CCL25 in generating CCR9(high) CD8 intestinal memory-phenotype T cells and the subsequent accumulation of these cells within effector sites. TCR-transgenic naive CD8 T cells were transferred into wild-type or CCL25-deficient hosts. Oral sensitization with Ag allowed these naive donor cells to efficiently differentiate into CCR9(high) memory-phenotype cells within the mesenteric lymph nodes of wild-type hosts. This differentiation event occurred with equal efficiency in the MLN of CCL25-deficient hosts, demonstrating that CCL25 is not required to induce the CCR9(high) memory phenotype in vivo. However, we found that CCL25 deficiency severely impaired the Ag-dependent accumulation of donor-derived CD8 T cells within both lamina propria and epithelium of the small intestine. Thus, although CCL25 is not necessary for generating memory-phenotype CD8 T cells with "gut-homing" properties, this chemokine is indispensable for their trafficking to the small intestine.