Imaging of the cross-presenting dendritic cell subsets in the skin-draining lymph node
Imaging of the cross-presenting dendritic cell subsets in the skin-draining lymph node
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DOI：
10.1073/pnas.1513607113
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发表时间：
2016-01-26
影响因子：
11.1
通讯作者：
Okada, Takaharu
中科院分区：
文献类型：
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作者：
Kitano, Masahiro;Yamazaki, Chihiro;Okada, Takaharu
树突状细胞（dc）是抗原呈递细胞，专门用于激活T细胞以引发效应T细胞功能。交叉呈递DC是一种能够向CD8(+) T细胞呈递抗原的DC亚群，在细胞毒性T细胞介导的针对微生物和癌症的免疫应答中发挥关键作用。虽然它们的重要性是已知的，但体内交叉呈现的dc的时空动态尚不完全清楚。在这里，我们研究了皮肤引流淋巴结（SDLNs）中的t细胞区，发现它被划分为表达趋化因子（C基序）受体1基因Xcr1的交叉呈递dc激活CD8(+) t细胞的区域和CD11b(+) dc激活CD4(+) t细胞的区域。SDLNs中表达xcr1的dc由两种不同的人群组成：迁移性（CD103(hi)） dc，它们从皮肤迁移而来，以及在淋巴结中发育的常驻（CD8 α (hi)） dc。为了表征这些不同DC群体在体内活化过程中与CD8(+) T细胞的动态相互作用，我们开发了一种光转换报告小鼠菌株，使我们能够清楚地看到表达xcr1的DC的迁移和常驻亚群。离开皮肤后，迁移的dc在3 d内浸润到SDLNs的深部t细胞区，这与它们在SDLNs中的半衰期相对应。活体双光子成像显示，在可溶性抗原免疫后，新到达的迁移dc比SDLNs中其他表达xcr1的dc更有效地与抗原特异性CD8(+) T细胞形成持续的偶联物。这些结果为迁移和常驻交叉呈递dc对CD8(+) t细胞活化的不同贡献提供了体内证据。
Dendritic cells (DCs) are antigen-presenting cells specialized for activating T cells to elicit effector T-cell functions. Cross-presenting DCs are a DC subset capable of presenting antigens to CD8(+) T cells and play critical roles in cytotoxic T-cell-mediated immune responses to microorganisms and cancer. Although their importance is known, the spatiotemporal dynamics of cross-presenting DCs in vivo are incompletely understood. Here, we study the T-cell zone in skin-draining lymph nodes (SDLNs) and find it is compartmentalized into regions for CD8(+) T-cell activation by cross-presenting DCs that express the chemokine (C motif) receptor 1 gene, Xcr1 and for CD4(+) T-cell activation by CD11b(+) DCs. Xcr1-expressing DCs in the SDLNs are composed of two different populations: migratory (CD103(hi)) DCs, which immigrate from the skin, and resident (CD8 alpha(hi)) DCs, which develop in the nodes. To characterize the dynamic interactions of these distinct DC populations with CD8(+) T cells during their activation in vivo, we developed a photoconvertible reporter mouse strain, which permits us to distinctively visualize the migratory and resident subsets of Xcr1-expressing DCs. After leaving the skin, migratory DCs infiltrated to the deep T-cell zone of the SDLNs over 3 d, which corresponded to their half-life in the SDLNs. Intravital two-photon imaging showed that after soluble antigen immunization, the newly arriving migratory DCs more efficiently form sustained conjugates with antigen-specific CD8(+) T cells than other Xcr1-expressing DCs in the SDLNs. These results offer in vivo evidence for differential contributions of migratory and resident cross-presenting DCs to CD8(+) T-cell activation.