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Roles of lymphatic endothelial cells expressing peripheral tissue antigens in CD4 T-cell tolerance induction
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2015 (English)In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 6, 6771Article in journal (Refereed) Published
Abstract [en]

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 beta-galactosidase (beta-gal) is expressed in LECs, beta-gal-specific CD8 Tcells undergo deletion via the PD-1/PD-L1 and LAG-3/MHC-II pathways. In contrast, LECs do not present endogenous b-gal in the context of MHC-II molecules to b-gal-specific CD4 T cells. Lack of presentation is independent of antigen localization, as membrane-bound haemagglutinin and I-Ea 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 b-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.

Place, publisher, year, edition, pages
2015. Vol. 6, 6771
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Immunology in the medical area
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URN: urn:nbn:se:uu:diva-255307DOI: 10.1038/ncomms7771ISI: 000353702500011PubMedID: 25857745OAI: oai:DiVA.org:uu-255307DiVA: diva2:822448
Available from: 2015-06-16 Created: 2015-06-15 Last updated: 2017-12-04Bibliographically approved

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Mäkinen, Taija

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