Imaging of the cross-presenting dendritic cell subsets in the skin-draining lymph node

Masahiro Kitano, Chihiro Yamazaki, Akiko Takumi, Takashi Ikeno, Hiroaki Hemmi, Noriko Takahashi, Kanako Shimizu, Scott E. Fraser, Katsuaki Hoshino, Tsuneyasu Kaisho, Takaharu Okada

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

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 (CD103hi) DCs, which immigrate from the skin, and resident (CD8αhi) 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.

Original languageEnglish
Pages (from-to)1044-1049
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number4
DOIs
Publication statusPublished - Jan 26 2016

Keywords

  • CD8 T cell
  • Cross-presentation
  • Dendritic cell
  • Intravital two-photon imaging
  • Photoconversion

ASJC Scopus subject areas

  • General

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    Kitano, M., Yamazaki, C., Takumi, A., Ikeno, T., Hemmi, H., Takahashi, N., Shimizu, K., Fraser, S. E., Hoshino, K., Kaisho, T., & Okada, T. (2016). Imaging of the cross-presenting dendritic cell subsets in the skin-draining lymph node. Proceedings of the National Academy of Sciences of the United States of America, 113(4), 1044-1049. https://doi.org/10.1073/pnas.1513607113