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派尔集合淋巴结树突状细胞对归巢至肠道的T细胞的选择性印记

Selective imprinting of gut-homing T cells by Peyer's patch dendritic cells.

作者信息

Mora J Rodrigo, Bono Maria Rosa, Manjunath N, Weninger Wolfgang, Cavanagh Lois L, Rosemblatt Mario, Von Andrian Ulrich H

机构信息

The Center for Blood Research and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.

出版信息

Nature. 2003 Jul 3;424(6944):88-93. doi: 10.1038/nature01726.

Abstract

Whereas naive T cells migrate only to secondary lymphoid organs, activation by antigen confers to T cells the ability to home to non-lymphoid sites. Activated effector/memory T cells migrate preferentially to tissues that are connected to the secondary lymphoid organs where antigen was first encountered. 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.

摘要

未成熟的T细胞仅迁移至二级淋巴器官,而抗原激活则赋予T细胞归巢至非淋巴组织的能力。活化的效应/记忆T细胞优先迁移至与首次遇到抗原的二级淋巴器官相连的组织。因此,口服抗原可诱导表达肠道归巢必需受体的效应/记忆细胞,即整合素α4β7和CCR9,后者是肠道相关趋化因子TECK/CCL25的受体(参考文献6、8、9)。我们在此表明,这种肠道嗜性的印记是由派尔集合淋巴结的树突状细胞介导的。派尔集合淋巴结、外周淋巴结和脾脏的树突状细胞对表达CD8的T细胞的刺激在T细胞中诱导了等效的活化标志物和效应活性,但只有派尔集合淋巴结的树突状细胞诱导了高水平的α4β7、对TECK的反应性以及归巢至小肠的能力。这些发现证实,派尔集合淋巴结的树突状细胞在T细胞上印记肠道归巢特异性,从而使效应/记忆细胞能够进入最有可能含有其同源抗原的解剖部位。

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