Dendritic cell immunization route determines CD8+ T cell trafficking to inflamed skin:: Role for tissue microenvironment and dendritic cells in establishment of T cell-homing subsets
Dendritic cell immunization route determines CD8+ T cell trafficking to inflamed skin:: Role for tissue microenvironment and dendritic cells in establishment of T cell-homing subsets
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DOI：
10.4049/jimmunol.172.2.857
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发表时间：
2004-01-15
影响因子：
4.4
通讯作者：
Martin, S
中科院分区：
文献类型：
--
作者：
Dudda, JC;Simon, JC;Martin, S
效应/记忆T细胞库分支在归巢亚群中选择性地转运到内脏或皮肤等器官。尽管CD8(+) T细胞是皮肤限制性免疫反应（如接触性超敏反应和黑色素瘤防御）的关键效应因子，但对皮肤归巢的关键因素知之甚少。在这项研究中，我们发现皮内注射而不是静脉注射骨髓来源的树突状细胞诱导皮肤归巢的CD8(+) T细胞在接触性超敏反应中表达上调e -选择素配体和效应功能。在没有进一步银接触的记忆期，皮肤归巢电位和e -选择素配体表达保持稳定。相反，i.p.注射诱导T细胞表达肠归巢整合素(4)(7)。尽管这些粘附分子的差异表达与免疫途径密切相关，但假设的皮肤归巢标记CCR4在所有条件下都短暂上调。有趣的是，来自不同组织的树突状细胞在体外有效地诱导T细胞上相应的归巢标记。我们的研究结果表明，组织微环境和树突状细胞在T细胞的组织选择性归巢指令中起着至关重要的作用，并证明朗格汉斯细胞专门针对炎症皮肤的T细胞。免疫学杂志，2004,17(2):857-863。
The effector/memory T cell pool branches in homing subsets selectively trafficking to organs such as gut or skin. Little is known about the critical factors in the generation of skin-homing CD8(+) T cells, although they are crucial effectors in skin-restricted immune responses such as contact hypersensitivity and melanoma defense. In this study, we show that intracutaneous, but not i.v. injection of bone marrow-derived dendritic cells induced skin-homing CD8(+) T cells with up-regulated E-selectin ligand expression and effector function in contact hypersensitivity. The skin-homing potential and E-selectin ligand expression remained stable in memory phase without further Ag contact. In contrast, i.p. injection induced T cells expressing the gut-homing integrin alpha(4)beta(7). Although differential expression of these adhesion molecules was strictly associated with the immunization route, the postulated skin-homing marker CCR4 was transiently up-regulated in all conditions. Interestingly, dendritic cells from different tissues effectively induced the corresponding homing markers on T cells in vitro. Our results suggest a crucial role for the tissue micro-environment and dendritic cells in the instruction of T cells for tissue-selective homing and demonstrate that Langerhans cells are specialized to target T cells to inflamed skin. The Journal of Immunology, 2004, 172: 857-863.