Dudda Jan C, Lembo Annalisa, Bachtanian Eva, Huehn Jochen, Siewert Christiane, Hamann Alf, Kremmer Elisabeth, Förster Reinhold, Martin Stefan F
Clinical Research Group Allergology, Department of Dermatology, University of Freiburg, Freiburg, Germany.
Eur J Immunol. 2005 Apr;35(4):1056-65. doi: 10.1002/eji.200425817.
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 alpha4beta7 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.
组织选择性归巢在初始T细胞被组织微环境和组织特异性树突状细胞（DC）激活的过程中得以确立。驱动T细胞归巢模式诱导和维持的因素在很大程度上仍不明确。在此我们表明，T细胞与从皮肤或小肠相关组织分离的CD11c(+) DC相互作用过程中产生的可溶性因子，可差异性地调节小鼠CD8(+) T细胞上相应组织选择性归巢受体（分别为E-选择素配体和α4β7整合素/CCR9）的表达。通过不同途径注射组织特异性DC可诱导T细胞表达具有相应局部组织微环境特征的归巢受体，这与DC的来源无关。这些数据表明了反式传递信号的重要作用。此外，DC可重新编程先前在体外极化以归巢至皮肤或小肠的T细胞上的归巢受体表达。重要的是，直接在体外刺激的皮肤归巢记忆T细胞也可被肠道DC重新编程为肠道归巢表型。我们的结果表明，效应T细胞和记忆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信号以及抑制信号的调控。
