MIGRATION PATTERNS OF DENDRITIC CELLS IN THE MOUSE - TRAFFIC FROM THE BLOOD, AND T-CELL-DEPENDENT AND T-CELL-INDEPENDENT ENTRY TO LYMPHOID-TISSUES
MIGRATION PATTERNS OF DENDRITIC CELLS IN THE MOUSE - TRAFFIC FROM THE BLOOD, AND T-CELL-DEPENDENT AND T-CELL-INDEPENDENT ENTRY TO LYMPHOID-TISSUES
复制标题
DOI：
10.1084/jem.167.2.632
复制
发表时间：
1988-02-01
影响因子：
15.3
通讯作者：
MORRIS, PJ
中科院分区：
文献类型：
--
作者：
KUPIECWEGLINSKI, JW;AUSTYN, JM;MORRIS, PJ
树突状细胞（DC）是原发性免疫应答的关键辅助细胞，它们可能是移植反应的重要刺激物，但对它们进入组织的运输知之甚少。我们研究了纯化的脾DC和~（111）铟-托酚酮标记的T淋巴细胞在同基因和异基因小鼠体内的迁移。首先，我们证明了DC可以从血液迁移到一些淋巴和非淋巴组织。静脉给药后，放射性标记的DC立即被隔离在肺中，但它们主动迁移到肝脏和脾脏，并在转移后3至24小时达到平衡水平。至少有一半的放射性标记积累在肝脏中，但脾脏是DC定位的主要部位，就比活性而言（单位组织重量的放射性标记）。DC不能从血流进入派尔集合淋巴结、肠系膜淋巴结和其他外周淋巴结。在脾切除的受体中也是如此，其中另外的脾寻求DC定量地转移到肝脏。相反，T细胞很容易归巢到正常小鼠的脾脏和淋巴结，并且在脾切除小鼠的这些组织中存在数量增加。因此，与T细胞不同，DC不能通过淋巴结从血液再循环到淋巴。然后，我们表明，DC从血液中迁移到脾脏是依赖于T细胞的存在：DC没有进入裸鼠的脾脏，但当它们与T细胞重建进入脾脏的数量类似于那些在正常胸腺小鼠。在裸鼠中，与脾切除受体一样，正常情况下进入脾脏的DC被定量转移到肝脏。这些发现表明DC存在脾-肝平衡，这可能类似于T细胞存在于脾和淋巴结之间。最后，我们跟踪了皮下足垫接种后放射性标记的DC通过传入神经的交通。DC积聚在腘淋巴结，但没有进一步迁移到腹股沟淋巴结。正常胸腺小鼠和裸鼠之间没有差异，表明与脾脏运输不同，该途径可能不需要T细胞。这些迁移模式不受主要组织相容性屏障的影响，并且仅在存活的DC中观察到，但在戊二醛固定的DC中未观察到。DC从血液中迁移的新途径的证明，以及进入淋巴组织的T依赖性和非T依赖性途径，对于炎症反应期间DC从血液进入非淋巴组织的运输以及淋巴外的产生具有重要意义免疫反应。
Dendritic cells (DC) are critical accessory cells for primary immune responses and they may be important stimulators of transplantation reactions, but little is known of their traffic into the tissues. We have studied the migration of purified splenic DC and T lymphocytes, labeled with 111Indium-tropolone, in syngeneic and allogeneic mice. First we demonstrate that DC can migrate from the blood into some lymphoid and nonlymphoid tissues. Immediately after intravenous administration, radiolabeled DC were sequestered in the lungs, but they actively migrated into the liver and spleen and reached equilibrium levels between 3 and 24 h after transfer. At least half of the radiolabel accumulated in the liver, but the spleen was the principal site of DC localization in terms of specific activity (radiolabel per weight of tissue). DC were unable to enter Peyer''s patches, or mesenteric and other peripheral lymph nodes from the bloodstream. This was also true in splenectomized recipients, where the otherwise spleen-seeking DC were quantitatively diverted to the liver. In contrast, T cells homed readily to the spleen and lymph nodes of normal mice and increased numbers were present in these tissues in splenectomized mice. Thus, unlike T cells, DC cannot recirculate from blood to lymph via the nodes. We then show that migration of DC from the blood into the spleen is dependent on the presence of T cells: DC did not enter the spleens of nude mice, but when they were reconstituted with T cells the numbers entering the spleen resembled those in euthymic mice. In nude mice, as in splenectomized recipients, the DC that would normally enter the spleen were quantitatively diverted to the liver. These findings suggest that there is a spleen-liver equilibrium for DC, that may be akin to that existing between spleen and lymph node for T cells. Finally, we followed the traffic of radiolabeled DC via the afferent lymphatics after subcutaneous footpad inoculation. DC accumulated in the popliteal nodes but did not migrate further to the inguinal nodes. There was no difference between euthymic and nude mice, showing that unlike traffic to the spleen, this route probably does not require T cells. These migration patterns were not affected by major histocompatibility barriers, and were only seen with viable, but not glutaraldehyde-fixed, DC. The demonstration of a novel migratory pathway for DC from the blood, together with T-dependent and -independent routes for entry to lymphoid tissues, has important implications for the traffic of DC from the blood into nonlymphoid tissues during inflammatory reactions and perhaps for the generation of extralymphoid immune responses.