CD40-CD40 ligand interactions in vivo regulate migration of antigen-bearing dendritic cells from the skin to draining lymph nodes
CD40-CD40 ligand interactions in vivo regulate migration of antigen-bearing dendritic cells from the skin to draining lymph nodes
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DOI：
10.1084/jem.191.11.2011
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发表时间：
2000-06-05
影响因子：
15.3
通讯作者：
Flores-Romo, L
中科院分区：
文献类型：
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作者：
Moodycliffe, AM;Shreedhar, V;Flores-Romo, L
虽然CD40-CD40配体的相互作用在体外对树突状细胞(DC)的各种功能很重要，但它们在体内的相关性尚不清楚。我们使用接触性超敏反应(CHS)模型系统分析了CD40配体/-小鼠的DC状态，该模型系统能够在体内评估DC的多种功能。皮肤切片免疫组织化学染色显示，未致敏的CD40L-/-小鼠与野生型C57BL/6小鼠相比，树突状表皮朗格汉斯细胞(LCS)的数量和形态无明显差异。然而，在CD40配体/-小鼠接触致敏后，LCS无法从皮肤中迁移出来，并且在引流淋巴结(DLN)中积聚的DC显著减少。此外，在引流致敏皮肤的淋巴结旁皮质区可检测到极少数携带抗原的树突状细胞。半抗原致敏后DC迁移的这种缺陷与CHS反应缺陷和皮肤肿瘤坏死因子-α的产生减少有关，并可通过注射重组的肿瘤坏死因子-α或激动型抗CD40单抗来纠正。因此，体内CD40-CD40配体的相互作用通过产生肿瘤坏死因子-α调节携带抗原的DC从皮肤向DLN的迁移，并在启动获得性T细胞介导的免疫中发挥重要作用。
Whereas CD40-CD40 ligand interactions are important for various dendritic cell (DC) functions in vitro, their in vivo relevance is unknown. We analyzed the DC status of CD40 ligand -/- mice using a contact hypersensitivity (CHS) model system that enables multiple functions of DCs to be assessed in vivo. Immunohistochemistry of skin sections revealed no differences in terms of numbers and morphology of dendritic epidermal Langerhans cells (LCs) in unsensitized CD40 ligand -/- mice as compared with wild-type C57BL/6 mice. However, after contact sensitization of CD40 ligand -/- mice, LCs failed to migrate out of the skin and substantially fewer DCs accumulated in draining lymph nodes (DLNs). Furthermore, very few antigen-bearing DCs could be detected in the paracortical region of lymph nodes draining sensitized skin. This defect in DC migration after hapten sensitization was associated with defective CHS responses and decreased cutaneous tumor necrosis factor (TNF)-alpha production and was corrected by injecting recombinant TNF-alpha or an agonistic anti-CD40 monoclonal antibody. Thus, CD40-CD40 ligand interactions in vivo regulate the migration of antigen-bearing DCs from the skin to DLNs via TNF-alpha production and play a vital role in the initiation of acquired T cell-mediated immunity.