Dendritic cells govern induction and reprogramming of polarized tissue-selective homing receptor patterns of T cells:: important roles for soluble factors and tissue microenvironments
Dendritic cells govern induction and reprogramming of polarized tissue-selective homing receptor patterns of T cells:: important roles for soluble factors and tissue microenvironments
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DOI：
10.1002/eji.200425817
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发表时间：
2005-04-01
影响因子：
5.4
通讯作者：
Martin, SF
中科院分区：
文献类型：
--
作者：
Dudda, JC;Lembo, A;Martin, SF
组织选择性归巢是在组织微环境和组织特异性树突状细胞（DC）激活幼稚T细胞期间建立的。驱动T细胞归巢模式的诱导和维持的因素在很大程度上仍然是未知的。在这里，我们表明，在T细胞与从皮肤或小的肿瘤相关组织分离的CD 11 c（+）DC相互作用过程中产生的可溶性因子差异性地调节小鼠CD 8（+）T细胞上相应的组织选择性归巢受体（分别为E-选择素配体和α 4 β 7整合素/CCR 9）的表达。通过不同途径注射组织特异性DC诱导具有相应局部组织微环境特征性归巢受体的T细胞，而与DC的来源无关。这些数据表明了一个重要的作用，在trans.此外，DC可以重新编程归巢受体表达T细胞先前在体外极化归巢到皮肤或小肠的信号。重要的是，直接离体刺激的皮肤归巢记忆T细胞也可以通过肠道DC重编程为肠道归巢表型。我们的研究结果表明，效应和记忆T细胞上的组织选择性归巢受体表达受来自DC和组织微环境的诱导和抑制信号的支配。
Tissue-selective homing is established during naive T cell activation by the tissue microenvironment and tissue-specific dendritic cells (DC). The factors driving induction and maintenance of T cell homing patterns are still largely unknown. Here we show that soluble factors produced during the interaction of T cells with CD11c(+) DC isolated from skin- or small intestine-associated tissues differentially modulate expression of the corresponding tissue-selective homing receptors (E-selectin ligands and alpha 4 beta 7 integrin/CCR9, respectively) on murine CD8(+) T cells. Injection of tissue-specific DC via different routes induces T cells with homing receptors characteristic of the corresponding local tissue microenvironment, independent of the origin of the DC. These data indicate an important role for signals delivered in trans. Moreover, DC can reprogram the homing receptor expression on T cells previously polarized in vitro for homing to skin or small intestine. Importantly, skin-homing memory T cells stimulated directly ex vivo can also be reprogrammed by intestinal DC to a gut-homing phenotype. Our results show that tissue-selective homing receptor expression on effector and memory T cells is governed by inductive as well as suppressive signals from both DC and tissue microenvironments.