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Roles of lymphatic endothelial cells expressing peripheral tissue antigens in CD4 T-cell tolerance induction

Author

Listed:
  • Sherin J. Rouhani

    (Carter Immunology Center, Immunology and Cancer Biology, University of Virginia School of Medicine)

  • Jacob D. Eccles

    (Carter Immunology Center, Immunology and Cancer Biology, University of Virginia School of Medicine)

  • Priscila Riccardi

    (Carter Immunology Center, Immunology and Cancer Biology, University of Virginia School of Medicine)

  • J. David Peske

    (Carter Immunology Center, Immunology and Cancer Biology, University of Virginia School of Medicine)

  • Eric F. Tewalt

    (Carter Immunology Center, Immunology and Cancer Biology, University of Virginia School of Medicine)

  • Jarish N. Cohen

    (Carter Immunology Center, Immunology and Cancer Biology, University of Virginia School of Medicine)

  • Roland Liblau

    (INSERM
    Centre National de la Recherche Scientifique
    Centre de Physiopathologie Toulouse–Purpan, Université de Toulouse, Université Paul Sabatier
    Centre Hospitalier Universitaire de Toulouse, Hôpital Purpan)

  • Taija Mäkinen

    (Genetics and Pathology, Rudbeck Laboratory, Uppsala University)

  • Victor H. Engelhard

    (Carter Immunology Center, Immunology and Cancer Biology, University of Virginia School of Medicine)

Abstract

Lymphatic endothelial cells (LECs) directly express peripheral tissue antigens and induce CD8 T-cell deletional tolerance. LECs express MHC-II molecules, suggesting they might also tolerize CD4 T cells. We demonstrate that when β-galactosidase (β-gal) is expressed in LECs, β-gal-specific CD8 T cells undergo deletion via the PD-1/PD-L1 and LAG-3/MHC-II pathways. In contrast, LECs do not present endogenous β-gal in the context of MHC-II molecules to β-gal-specific CD4 T cells. Lack of presentation is independent of antigen localization, as membrane-bound haemagglutinin and I-Eα are also not presented by MHC-II molecules. LECs express invariant chain and cathepsin L, but not H2-M, suggesting that they cannot load endogenous antigenic peptides onto MHC-II molecules. Importantly, LECs transfer β-gal to dendritic cells, which subsequently present it to induce CD4 T-cell anergy. Therefore, LECs serve as an antigen reservoir for CD4 T-cell tolerance, and MHC-II molecules on LECs are used to induce CD8 T-cell tolerance via LAG-3.

Suggested Citation

  • Sherin J. Rouhani & Jacob D. Eccles & Priscila Riccardi & J. David Peske & Eric F. Tewalt & Jarish N. Cohen & Roland Liblau & Taija Mäkinen & Victor H. Engelhard, 2015. "Roles of lymphatic endothelial cells expressing peripheral tissue antigens in CD4 T-cell tolerance induction," Nature Communications, Nature, vol. 6(1), pages 1-13, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7771
    DOI: 10.1038/ncomms7771
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    Cited by:

    1. João Cardeira-da-Silva & Qianchen Wang & Pooja Sagvekar & Janita Mintcheva & Stephan Latting & Stefan Günther & Radhan Ramadass & Michail Yekelchyk & Jens Preussner & Mario Looso & Jan Philipp Junker , 2024. "Antigen presentation plays positive roles in the regenerative response to cardiac injury in zebrafish," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    2. Nieves Montenegro-Navarro & Claudia García-Báez & Melissa García-Caballero, 2023. "Molecular and metabolic orchestration of the lymphatic vasculature in physiology and pathology," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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