Selective imprinting of gut-homing T cells by Peyer's patch dendritic cells
Selective imprinting of gut-homing T cells by Peyer's patch dendritic cells
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DOI：
10.1038/nature01726
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发表时间：
2003-07-03
期刊：
影响因子：
64.8
通讯作者：
von Andrian, UH
中科院分区：
文献类型：
--
作者：
Mora, JR;Bono, MR;von Andrian, UH
幼稚T细胞仅迁移至次级淋巴器官（1，2），而抗原的激活赋予T细胞归巢至非淋巴部位的能力（3，4）。活化的效应/记忆T细胞优先迁移到与第一次遇到抗原的次级淋巴器官相连的组织（5-7）。因此，口服抗原诱导表达肠归巢必需受体的效应/记忆细胞，即整合素α 4 β 7和CCR 9，肠相关趋化因子TECK/CCL 25的受体（参考文献6，8，9）。在这里，我们表明，这种印记的肠道向性介导的树突状细胞从派尔集合淋巴结。来自派尔集合淋巴结、外周淋巴结和脾脏的树突状细胞刺激表达CD 8的T细胞诱导T细胞中的等效活化标志物和效应物活性，但只有派尔集合淋巴结树突状细胞诱导高水平的α 4 β 7、对TECK的反应性和归巢至小肠的能力。这些发现证实派尔斑树突状细胞在T细胞上印记肠道归巢特异性，从而许可效应/记忆细胞进入最可能含有其同源抗原的解剖部位。
Whereas naive T cells migrate only to secondary lymphoid organs(1,2), activation by antigen confers to T cells the ability to home to non-lymphoid sites(3,4). Activated effector/memory T cells migrate preferentially to tissues that are connected to the secondary lymphoid organs where antigen was first encountered(5-7). Thus, oral antigens induce effector/memory cells that express essential receptors for intestinal homing, namely the integrin alpha4beta7 and CCR9, the receptor for the gut-associated chemokine TECK/CCL25 (refs 6, 8, 9). Here we show that this imprinting of gut tropism is mediated by dendritic cells from Peyer's patches. Stimulation of CD8-expressing T cells by dendritic cells from Peyer's patches, peripheral lymph nodes and spleen induced equivalent activation markers and effector activity in T cells, but only Peyer's patch dendritic cells induced high levels of alpha4beta7, responsiveness to TECK and the ability to home to the small intestine. These findings establish that Peyer's patch dendritic cells imprint gut-homing specificity on T cells, and thus license effector/memory cells to access anatomical sites most likely to contain their cognate antigen.