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Plasmacytoid dendritic cells induce tolerance predominantly by cargoing antigen to lymph nodes.

ABSTRACT: Plasmacytoid dendritic cells (pDCs) have been shown to induce tolerance to innocuous antigens. Their migratory properties allow them to take up antigens from the periphery and transport them to the draining lymph nodes or to the thymus. However, pDC-T-cell interaction in the primary and secondary lymphoid organs still remains poorly defined. In this study, we show that resting pDCs loaded with exogenous antigen could induce tolerance when transferred intralymphatically into a single lymph node of wild-type C57BL/6 mice. However, this was a result of antigen transfer from pDCs to endogenous antigen presenting cells and subsequent abortive proliferation of cognate CD4⁺ T cells. pDCs could not directly induce the proliferation of CD4⁺ T cells, as observed in mice lacking MHC class II gene. Moreover, pDCs failed to make physical contacts with OT-II cells as revealed by two-photon imaging. Thus, the role of resting pDCs in tolerance induction seems to be independent of its direct interaction with cognate CD4⁺ T cells.

SUBMITTER: Kohli K

PROVIDER: S-EPMC5129535 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Plasmacytoid dendritic cells induce tolerance predominantly by cargoing antigen to lymph nodes.

Kohli Karan K Janssen Anika A Förster Reinhold R

European journal of immunology 20161018 11

Plasmacytoid dendritic cells (pDCs) have been shown to induce tolerance to innocuous antigens. Their migratory properties allow them to take up antigens from the periphery and transport them to the draining lymph nodes or to the thymus. However, pDC-T-cell interaction in the primary and secondary lymphoid organs still remains poorly defined. In this study, we show that resting pDCs loaded with exogenous antigen could induce tolerance when transferred intralymphatically into a single lymph node o ...[more]

PMID: 27592607

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Project description:Recent clinical observations have emphasized the critical role that the spatial organization of immune cells in lymphoid structures plays in the success of cancer immunotherapy and patient survival. However, implementing sequential chromogenic IHC (scIHC) to analyze multiple biomarkers on a single tissue section has been limited because of a lack of a standardized, rigorous guide to the development of customized biomarker panels and a need for user-friendly analysis pipelines that can extract meaningful data. In this context, we provide a comprehensive guide for the development of novel biomarker panels for scIHC, using practical examples and illustrations to highlight the most common complications that can arise during the setup of a new biomarker panel, and provide detailed instructions on how to prevent and detect cross-reactivity between secondary reagents and carryover between detection antibodies. We also developed a novel analysis pipeline based on non-rigid tissue deformation correction, Cellpose-inspired automated cell segmentation, and computational network masking of low-quality data. We applied this biomarker panel and pipeline to study regional lymph nodes from patients with head and neck cancer, identifying novel contact interactions between plasmablasts and plasmacytoid dendritic cells in vivo. Given that Toll-like receptors, which are highly expressed in plasmacytoid dendritic cells, play a key role in vaccine efficacy, the significance of this cell-cell interaction decisively warrants further studies. In summary, this work provides a streamlined approach to the development of customized biomarker panels for scIHC that will ultimately improve our understanding of immune responses in cancer.SignificanceWe present a comprehensive guide for developing customized biomarker panels to investigate cell-cell interactions in the context of immune responses in cancer. This approach revealed novel contact interactions between plasmablasts and plasmacytoid dendritic cells in lymph nodes from patients with head and neck cancer.

Dataset Information

Plasmacytoid dendritic cells induce tolerance predominantly by cargoing antigen to lymph nodes.

Publications

Plasmacytoid dendritic cells induce tolerance predominantly by cargoing antigen to lymph nodes.

Similar Datasets

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